Sangram S. Sisodia

Research Summary
Alzheimer’s disease (AD), a prevalent, adult-onset, neurodegenerative disease, is clinically characterized by progressive impairments in cognition and memory. These clinical features are accompanied by characteristic histological changes in the brain, including neuronal loss, extracellular deposition of fibrillogenic Ab peptides in senile plaques and intracellular neurofibrillary tangles. The principal risk factors for AD are age and inheritance of mutant genes, or polymorphic alleles that predispose individuals to late-onset disease. Over the past 20 years, my laboratory has focused on examining the cellular and molecular biology of the b-amyloid precursor protein (APP), or presenilins (PS1 and PS2), molecules that are mutated in pedigrees with autosomal dominant, familial forms of Alzheimer's disease (FAD). The function(s) of APP in the central nervous system (CNS) are still not fully understood, but we have demonstrated that APP is subject to rapid anterograde axonal transport and subject to proteolytic processing at, or near, terminal fields. In collaboration with Robert Malinow at UCSD, we have also shown that synaptic activity modulates APP processing and Ab production, and that both axonal and dendritic release of these peptides alter spine dynamics and glutamatergic neurotransmission. Our current efforts are focused on clarifying the dynamics and regulation of APP trafficking and processing cultured neurons and hippocampal slices using recombinant lentiviral-driven APP-GFP chimeras and live cell imaging approaches. In order to assess the normal function of PS, we have used gene targeting strategies; PS1-deficient animals die in late embryogenesis due to defective Notch signaling that is in large part, the result of failed intramembranous, “g-secretase” processing of a membrane-bound Notch substrates. This “g-secretase” activity is also responsible for liberating Ab peptides from membrane-bound APP derivatives. We, and others, have provided genetic and biochemical evidence has revealed that PS associates with nicastrin (NCT), APH-1 and PEN-2 in high molecular weight complexes, and our current efforts are aimed at understanding the temporal assembly of these membrane proteins, the nature of subunit interactions and the enzymatic mechanism(s) by which the complex promotes “g-secretase” processing of Notch, APP and other type 1 membrane proteins. A significant effort of our laboratory has been to develop and characterize transgenic animals that express FAD-linked variants of PS1 and APP to clarify the underlying biochemical and pathophysiological alterations that cause AD. We have exploited these animals, as well as animals in which we have conditionally inactivated PS, to clarify issues relevant to axonal trafficking of membrane proteins, neurodegeneration, neuronal vulnerability, gene expression and APP/Ab metabolism. A significant effort in our laboratory is focused on understanding the cell non-autonomous effects of FAD-linked mutant PS1 expression on hippocampal neurogenesis. Our future studies will focus heavily on the mechanisms that are responsible for the observed effects using temporal and system-specific conditional gene inactivation approaches. Extending our demonstration that enriched environments and exercise modulates Ab metabolism and deposition in vivo, our ongoing efforts are focused on the role of polypeptides encoded by genes that are selectively regulated in these settings. Finally, we have been exploring the impact of the microbiome in modulation of amyloid deposition in mouse models of AD. In summary, my research program is designed to integrate genetic, neurobiologic, molecular and cellular information to clarify the normal biology of APP and PS and the mechanisms by which mutant genes cause AD. The value of animal models that recapitulate some features of the human disease have, and will be of enormous value for addressing issues relevant to the selective vulnerability of specific CNS systems, the pathophysiological sequelae and ultimately, will provide opportunities to explore mechanism-based therapeutic strategies.
Biosciences Graduate Program Association
  1. Veetil AT, Zou J, Henderson KW, Jani MS, Shaik SM, Sisodia SS, Hale ME, Krishnan Y. DNA-based fluorescent probes of NOS2 activity in live brains. Proc Natl Acad Sci U S A. 2020 06 30; 117(26):14694-14702. View in: PubMed

  2. Cable J, Holtzman DM, Hyman BT, Tansey MG, Colonna M, Kellis M, Brinton RD, Albert M, Wellington CL, Sisodia SS, Tanzi RE. Alternatives to amyloid for Alzheimer's disease therapies-a symposium report. Ann N Y Acad Sci. 2020 09; 1475(1):3-14. View in: PubMed

  3. Dodiya HB, Frith M, Sidebottom A, Cao Y, Koval J, Chang E, Sisodia SS. Synergistic depletion of gut microbial consortia, but not individual antibiotics, reduces amyloidosis in APPPS1-21 Alzheimer's transgenic mice. Sci Rep. 2020 05 18; 10(1):8183. View in: PubMed

  4. Zhang X, Zhang C, Prokopenko D, Liang Y, Han W, Tanzi RE, Sisodia SS. Negative evidence for a role of APH1B T27I variant in Alzheimer's disease. Hum Mol Genet. 2020 Apr 15; 29(6):955-966. View in: PubMed

  5. Ortega-Martinez S, Palla N, Zhang X, Lipman E, Sisodia SS. Deficits in Enrichment-Dependent Neurogenesis and Enhanced Anxiety Behaviors Mediated by Expression of Alzheimer's Disease-Linked Ps1 Variants Are Rescued by Microglial Depletion. J Neurosci. 2019 08 21; 39(34):6766-6780. View in: PubMed

  6. Dodiya HB, Kuntz T, Shaik SM, Baufeld C, Leibowitz J, Zhang X, Gottel N, Zhang X, Butovsky O, Gilbert JA, Sisodia SS. Sex-specific effects of microbiome perturbations on cerebral Aß amyloidosis and microglia phenotypes. J Exp Med. 2019 07 01; 216(7):1542-1560. View in: PubMed

  7. Minter MR, Hinterleitner R, Meisel M, Zhang C, Leone V, Zhang X, Oyler-Castrillo P, Zhang X, Musch MW, Shen X, Jabri B, Chang EB, Tanzi RE, Sisodia SS. Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APPSWE/PS1?E9 murine model of Alzheimer's disease. Sci Rep. 2017 09 05; 7(1):10411. View in: PubMed

  8. Füger P, Hefendehl JK, Veeraraghavalu K, Wendeln AC, Schlosser C, Obermüller U, Wegenast-Braun BM, Neher JJ, Martus P, Kohsaka S, Thunemann M, Feil R, Sisodia SS, Skodras A, Jucker M. Microglia turnover with aging and in an Alzheimer's model via long-term in vivo single-cell imaging. Nat Neurosci. 2017 Oct; 20(10):1371-1376. View in: PubMed

  9. Veetil AT, Chakraborty K, Xiao K, Minter MR, Sisodia SS, Krishnan Y. Cell-targetable DNA nanocapsules for spatiotemporal release of caged bioactive small molecules. Nat Nanotechnol. 2017 12; 12(12):1183-1189. View in: PubMed

  10. Minter MR, Zhang C, Leone V, Ringus DL, Zhang X, Oyler-Castrillo P, Musch MW, Liao F, Ward JF, Holtzman DM, Chang EB, Tanzi RE, Sisodia SS. Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer's disease. Sci Rep. 2016 07 21; 6:30028. View in: PubMed

  11. Zhang X, Sullivan E, Scimeca M, Wu X, Li YM, Sisodia SS. Evidence That the "Lid" Domain of Nicastrin Is Not Essential for Regulating ?-Secretase Activity. J Biol Chem. 2016 Mar 25; 291(13):6748-53. View in: PubMed

  12. Zhang X, Yu CJ, Sisodia SS. The topology of pen-2, a ?-secretase subunit, revisited: evidence for a reentrant loop and a single pass transmembrane domain. Mol Neurodegener. 2015 Aug 22; 10:39. View in: PubMed

  13. Butkinaree C, Canuel M, Essalmani R, Poirier S, Benjannet S, Asselin MC, Roubtsova A, Hamelin J, Marcinkiewicz J, Chamberland A, Guillemot J, Mayer G, Sisodia SS, Jacob Y, Prat A, Seidah NG. Amyloid Precursor-like Protein 2 and Sortilin Do Not Regulate the PCSK9 Convertase-mediated Low Density Lipoprotein Receptor Degradation but Interact with Each Other. J Biol Chem. 2015 Jul 24; 290(30):18609-20. View in: PubMed

  14. Zhang X, Hoey R, Koide A, Dolios G, Paduch M, Nguyen P, Wu X, Li Y, Wagner SL, Wang R, Koide S, Sisodia SS. A synthetic antibody fragment targeting nicastrin affects assembly and trafficking of ?-secretase. J Biol Chem. 2014 Dec 12; 289(50):34851-61. View in: PubMed

  15. Zhang X, Sisodia SS. Acne inversa caused by missense mutations in NCSTN is not fully compatible with impairments in Notch signaling. J Invest Dermatol. 2015 Feb; 135(2):618-620. View in: PubMed

  16. DeBoer SR, Dolios G, Wang R, Sisodia SS. Differential release of ß-amyloid from dendrite- versus axon-targeted APP. J Neurosci. 2014 Sep 10; 34(37):12313-27. View in: PubMed

  17. Villa JC, Chiu D, Brandes AH, Escorcia FE, Villa CH, Maguire WF, Hu CJ, de Stanchina E, Simon MC, Sisodia SS, Scheinberg DA, Li YM. Nontranscriptional role of Hif-1a in activation of ?-secretase and notch signaling in breast cancer. Cell Rep. 2014 Aug 21; 8(4):1077-92. View in: PubMed

  18. Veeraraghavalu K, Zhang C, Zhang X, Tanzi RE, Sisodia SS. Age-dependent, non-cell-autonomous deposition of amyloid from synthesis of ß-amyloid by cells other than excitatory neurons. J Neurosci. 2014 Mar 05; 34(10):3668-73. View in: PubMed

  19. Wagner SL, Zhang C, Cheng S, Nguyen P, Zhang X, Rynearson KD, Wang R, Li Y, Sisodia SS, Mobley WC, Tanzi RE. Soluble ?-secretase modulators selectively inhibit the production of the 42-amino acid amyloid ß peptide variant and augment the production of multiple carboxy-truncated amyloid ß species. Biochemistry. 2014 Feb 04; 53(4):702-13. View in: PubMed

  20. Veeraraghavalu K, Choi SH, Zhang X, Sisodia SS. Endogenous expression of FAD-linked PS1 impairs proliferation, neuronal differentiation and survival of adult hippocampal progenitors. Mol Neurodegener. 2013 Oct 20; 8:41. View in: PubMed

  21. Veeraraghavalu K, Zhang C, Miller S, Hefendehl JK, Rajapaksha TW, Ulrich J, Jucker M, Holtzman DM, Tanzi RE, Vassar R, Sisodia SS. Comment on "ApoE-directed therapeutics rapidly clear ß-amyloid and reverse deficits in AD mouse models". Science. 2013 May 24; 340(6135):924-f. View in: PubMed

  22. Veeraraghavalu K, Sisodia SS. Mutant presenilin 1 expression in excitatory neurons impairs enrichment-mediated phenotypes of adult hippocampal progenitor cells. Proc Natl Acad Sci U S A. 2013 May 28; 110(22):9148-53. View in: PubMed

  23. Crump CJ, Castro SV, Wang F, Pozdnyakov N, Ballard TE, Sisodia SS, Bales KR, Johnson DS, Li YM. BMS-708,163 targets presenilin and lacks notch-sparing activity. Biochemistry. 2012 Sep 18; 51(37):7209-11. View in: PubMed

  24. Zhang X, Garbett K, Veeraraghavalu K, Wilburn B, Gilmore R, Mirnics K, Sisodia SS. A role for presenilins in autophagy revisited: normal acidification of lysosomes in cells lacking PSEN1 and PSEN2. J Neurosci. 2012 Jun 20; 32(25):8633-48. View in: PubMed

  25. Zhang X, Hoey RJ, Lin G, Koide A, Leung B, Ahn K, Dolios G, Paduch M, Ikeuchi T, Wang R, Li YM, Koide S, Sisodia SS. Identification of a tetratricopeptide repeat-like domain in the nicastrin subunit of ?-secretase using synthetic antibodies. Proc Natl Acad Sci U S A. 2012 May 29; 109(22):8534-9. View in: PubMed

  26. Haass C, Kaether C, Thinakaran G, Sisodia S. Trafficking and proteolytic processing of APP. Cold Spring Harb Perspect Med. 2012 May; 2(5):a006270. View in: PubMed

  27. Li T, Li YM, Ahn K, Price DL, Sisodia SS, Wong PC. Increased expression of PS1 is sufficient to elevate the level and activity of ?-secretase in vivo. PLoS One. 2011; 6(11):e28179. View in: PubMed

  28. Brunholz S, Sisodia S, Lorenzo A, Deyts C, Kins S, Morfini G. Axonal transport of APP and the spatial regulation of APP cleavage and function in neuronal cells. Exp Brain Res. 2012 Apr; 217(3-4):353-64. View in: PubMed

  29. Prinz M, Priller J, Sisodia SS, Ransohoff RM. Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat Neurosci. 2011 Sep 27; 14(10):1227-35. View in: PubMed

  30. Renzi F, Zhang X, Rice WJ, Torres-Arancivia C, Gomez-Llorente Y, Diaz R, Ahn K, Yu C, Li YM, Sisodia SS, Ubarretxena-Belandia I. Structure of gamma-secretase and its trimeric pre-activation intermediate by single-particle electron microscopy. J Biol Chem. 2011 Jun 17; 286(24):21440-9. View in: PubMed

  31. Ahn K, Shelton CC, Tian Y, Zhang X, Gilchrist ML, Sisodia SS, Li YM. Activation and intrinsic gamma-secretase activity of presenilin 1. Proc Natl Acad Sci U S A. 2010 Dec 14; 107(50):21435-40. View in: PubMed

  32. Norstrom EM, Zhang C, Tanzi R, Sisodia SS. Identification of NEEP21 as a ß-amyloid precursor protein-interacting protein in vivo that modulates amyloidogenic processing in vitro. J Neurosci. 2010 Nov 17; 30(46):15677-85. View in: PubMed

  33. Kounnas MZ, Danks AM, Cheng S, Tyree C, Ackerman E, Zhang X, Ahn K, Nguyen P, Comer D, Mao L, Yu C, Pleynet D, Digregorio PJ, Velicelebi G, Stauderman KA, Comer WT, Mobley WC, Li YM, Sisodia SS, Tanzi RE, Wagner SL. Modulation of gamma-secretase reduces beta-amyloid deposition in a transgenic mouse model of Alzheimer's disease. Neuron. 2010 Sep 09; 67(5):769-80. View in: PubMed

  34. Veeraraghavalu K, Choi SH, Zhang X, Sisodia SS. Presenilin 1 mutants impair the self-renewal and differentiation of adult murine subventricular zone-neuronal progenitors via cell-autonomous mechanisms involving notch signaling. J Neurosci. 2010 May 19; 30(20):6903-15. View in: PubMed

  35. Veeraraghavalu K, Choi SH, Sisodia SS. Expression of familial Alzheimer's disease-linked human presenilin 1 variants impair enrichment-induced adult hippocampal neurogenesis. Neurodegener Dis. 2010; 7(1-3):46-9. View in: PubMed

  36. Wei W, Nguyen LN, Kessels HW, Hagiwara H, Sisodia S, Malinow R. Amyloid beta from axons and dendrites reduces local spine number and plasticity. Nat Neurosci. 2010 Feb; 13(2):190-6. View in: PubMed

  37. Choi SH, Li Y, Parada LF, Sisodia SS. Regulation of hippocampal progenitor cell survival, proliferation and dendritic development by BDNF. Mol Neurodegener. 2009 Dec 21; 4:52. View in: PubMed

  38. Meier M, Kennedy-Darling J, Choi SH, Norstrom EM, Sisodia SS, Ismagilov RF. Plug-based microfluidics with defined surface chemistry to miniaturize and control aggregation of amyloidogenic peptides. Angew Chem Int Ed Engl. 2009; 48(8):1487-9. View in: PubMed

  39. Placanica L, Tarassishin L, Yang G, Peethumnongsin E, Kim SH, Zheng H, Sisodia SS, Li YM. Pen2 and presenilin-1 modulate the dynamic equilibrium of presenilin-1 and presenilin-2 gamma-secretase complexes. J Biol Chem. 2009 Jan 30; 284(5):2967-77. View in: PubMed

  40. Tamboli IY, Prager K, Thal DR, Thelen KM, Dewachter I, Pietrzik CU, St George-Hyslop P, Sisodia SS, De Strooper B, Heneka MT, Filippov MA, Müller U, van Leuven F, Lütjohann D, Walter J. Loss of gamma-secretase function impairs endocytosis of lipoprotein particles and membrane cholesterol homeostasis. J Neurosci. 2008 Nov 12; 28(46):12097-106. View in: PubMed

  41. Mirnics K, Norstrom EM, Garbett K, Choi SH, Zhang X, Ebert P, Sisodia SS. Molecular signatures of neurodegeneration in the cortex of PS1/PS2 double knockout mice. Mol Neurodegener. 2008 Oct 03; 3:14. View in: PubMed

  42. Choi SH, Veeraraghavalu K, Lazarov O, Marler S, Ransohoff RM, Ramirez JM, Sisodia SS. Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation. Neuron. 2008 Aug 28; 59(4):568-80. View in: PubMed

  43. Vetrivel KS, Zhang X, Meckler X, Cheng H, Lee S, Gong P, Lopes KO, Chen Y, Iwata N, Yin KJ, Lee JM, Parent AT, Saido TC, Li YM, Sisodia SS, Thinakaran G. Evidence that CD147 modulation of beta-amyloid (Abeta) levels is mediated by extracellular degradation of secreted Abeta. J Biol Chem. 2008 Jul 11; 283(28):19489-98. View in: PubMed

  44. Kim J, Kleizen B, Choy R, Thinakaran G, Sisodia SS, Schekman RW. Biogenesis of gamma-secretase early in the secretory pathway. J Cell Biol. 2007 Dec 03; 179(5):951-63. View in: PubMed

  45. Kaneko H, Kakita A, Kasuga K, Nozaki H, Ishikawa A, Miyashita A, Kuwano R, Ito G, Iwatsubo T, Takahashi H, Nishizawa M, Onodera O, Sisodia SS, Ikeuchi T. Enhanced accumulation of phosphorylated alpha-synuclein and elevated beta-amyloid 42/40 ratio caused by expression of the presenilin-1 deltaT440 mutant associated with familial Lewy body disease and variant Alzheimer's disease. J Neurosci. 2007 Nov 28; 27(48):13092-7. View in: PubMed

  46. Chen Q, Nakajima A, Choi SH, Xiong X, Sisodia SS, Tang YP. Adult neurogenesis is functionally associated with AD-like neurodegeneration. Neurobiol Dis. 2008 Feb; 29(2):316-26. View in: PubMed

  47. Im H, Manolopoulou M, Malito E, Shen Y, Zhao J, Neant-Fery M, Sun CY, Meredith SC, Sisodia SS, Leissring MA, Tang WJ. Structure of substrate-free human insulin-degrading enzyme (IDE) and biophysical analysis of ATP-induced conformational switch of IDE. J Biol Chem. 2007 Aug 31; 282(35):25453-63. View in: PubMed

  48. Lazarov O, Morfini GA, Pigino G, Gadadhar A, Chen X, Robinson J, Ho H, Brady ST, Sisodia SS. Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer's disease-linked mutant presenilin 1. J Neurosci. 2007 Jun 27; 27(26):7011-20. View in: PubMed

  49. Choi SH, Leight SN, Lee VM, Li T, Wong PC, Johnson JA, Saraiva MJ, Sisodia SS. Accelerated Abeta deposition in APPswe/PS1deltaE9 mice with hemizygous deletions of TTR (transthyretin). J Neurosci. 2007 Jun 27; 27(26):7006-10. View in: PubMed

  50. Peng CY, Yajima H, Burns CE, Zon LI, Sisodia SS, Pfaff SL, Sharma K. Notch and MAML signaling drives Scl-dependent interneuron diversity in the spinal cord. Neuron. 2007 Mar 15; 53(6):813-27. View in: PubMed

  51. Hsieh H, Boehm J, Sato C, Iwatsubo T, Tomita T, Sisodia S, Malinow R. AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron. 2006 Dec 07; 52(5):831-43. View in: PubMed

  52. Thinakaran G, Sisodia SS. Presenilins and Alzheimer disease: the calcium conspiracy. Nat Neurosci. 2006 Nov; 9(11):1354-5. View in: PubMed

  53. Kim SH, Tang YP, Sisodia SS. Abeta star: a light onto synaptic dysfunction? Nat Med. 2006 Jul; 12(7):760-1; discussion 761. View in: PubMed

  54. Cai D, Netzer WJ, Zhong M, Lin Y, Du G, Frohman M, Foster DA, Sisodia SS, Xu H, Gorelick FS, Greengard P. Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid formation. Proc Natl Acad Sci U S A. 2006 Feb 07; 103(6):1941-6. View in: PubMed

  55. Cai D, Zhong M, Wang R, Netzer WJ, Shields D, Zheng H, Sisodia SS, Foster DA, Gorelick FS, Xu H, Greengard P. Phospholipase D1 corrects impaired betaAPP trafficking and neurite outgrowth in familial Alzheimer's disease-linked presenilin-1 mutant neurons. Proc Natl Acad Sci U S A. 2006 Feb 07; 103(6):1936-40. View in: PubMed

  56. Lazarov O, Peterson LD, Peterson DA, Sisodia SS. Expression of a familial Alzheimer's disease-linked presenilin-1 variant enhances perforant pathway lesion-induced neuronal loss in the entorhinal cortex. J Neurosci. 2006 Jan 11; 26(2):429-34. View in: PubMed

  57. Unger T, Korade Z, Lazarov O, Terrano D, Schor NF, Sisodia SS, Mirnics K. Transcriptome differences between the frontal cortex and hippocampus of wild-type and humanized presenilin-1 transgenic mice. Am J Geriatr Psychiatry. 2005 Dec; 13(12):1041-51. View in: PubMed

  58. Unger T, Korade Z, Lazarov O, Terrano D, Sisodia SS, Mirnics K. True and false discovery in DNA microarray experiments: transcriptome changes in the hippocampus of presenilin 1 mutant mice. Methods. 2005 Nov; 37(3):261-73. View in: PubMed

  59. Perez SE, Lazarov O, Koprich JB, Chen EY, Rodriguez-Menendez V, Lipton JW, Sisodia SS, Mufson EJ. Nigrostriatal dysfunction in familial Alzheimer's disease-linked APPswe/PS1DeltaE9 transgenic mice. J Neurosci. 2005 Nov 02; 25(44):10220-9. View in: PubMed

  60. Kim SH, Sisodia SS. Evidence that the "NF" motif in transmembrane domain 4 of presenilin 1 is critical for binding with PEN-2. J Biol Chem. 2005 Dec 23; 280(51):41953-66. View in: PubMed

  61. Mirnics ZK, Yan C, Portugal C, Kim TW, Saragovi HU, Sisodia SS, Mirnics K, Schor NF. P75 neurotrophin receptor regulates expression of neural cell adhesion molecule 1. Neurobiol Dis. 2005 Dec; 20(3):969-85. View in: PubMed

  62. Vetrivel KS, Cheng H, Kim SH, Chen Y, Barnes NY, Parent AT, Sisodia SS, Thinakaran G. Spatial segregation of gamma-secretase and substrates in distinct membrane domains. J Biol Chem. 2005 Jul 08; 280(27):25892-900. View in: PubMed

  63. Lazarov O, Robinson J, Tang YP, Hairston IS, Korade-Mirnics Z, Lee VM, Hersh LB, Sapolsky RM, Mirnics K, Sisodia SS. Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell. 2005 Mar 11; 120(5):701-13. View in: PubMed

  64. Lazarov O, Morfini GA, Lee EB, Farah MH, Szodorai A, DeBoer SR, Koliatsos VE, Kins S, Lee VM, Wong PC, Price DL, Brady ST, Sisodia SS. Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited. J Neurosci. 2005 Mar 02; 25(9):2386-95. View in: PubMed

  65. Mirnics K, Korade Z, Arion D, Lazarov O, Unger T, Macioce M, Sabatini M, Terrano D, Douglass KC, Schor NF, Sisodia SS. Presenilin-1-dependent transcriptome changes. J Neurosci. 2005 Feb 09; 25(6):1571-8. View in: PubMed

  66. Parent AT, Barnes NY, Taniguchi Y, Thinakaran G, Sisodia SS. Presenilin attenuates receptor-mediated signaling and synaptic function. J Neurosci. 2005 Feb 09; 25(6):1540-9. View in: PubMed

  67. Kim SH, Sisodia SS. A sequence within the first transmembrane domain of PEN-2 is critical for PEN-2-mediated endoproteolysis of presenilin 1. J Biol Chem. 2005 Jan 21; 280(3):1992-2001. View in: PubMed

  68. Kim SH, Yin YI, Li YM, Sisodia SS. Evidence that assembly of an active gamma-secretase complex occurs in the early compartments of the secretory pathway. J Biol Chem. 2004 Nov 19; 279(47):48615-9. View in: PubMed

  69. Herms J, Anliker B, Heber S, Ring S, Fuhrmann M, Kretzschmar H, Sisodia S, Müller U. Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members. EMBO J. 2004 Oct 13; 23(20):4106-15. View in: PubMed

  70. Louvi A, Sisodia SS, Grove EA. Presenilin 1 in migration and morphogenesis in the central nervous system. Development. 2004 Jul; 131(13):3093-105. View in: PubMed

  71. Mirnics ZK, Mirnics K, Terrano D, Lewis DA, Sisodia SS, Schor NF. DNA microarray profiling of developing PS1-deficient mouse brain reveals complex and coregulated expression changes. Mol Psychiatry. 2003 Oct; 8(10):863-78. View in: PubMed

  72. Taniguchi Y, Kim SH, Sisodia SS. Presenilin-dependent "gamma-secretase" processing of deleted in colorectal cancer (DCC). J Biol Chem. 2003 Aug 15; 278(33):30425-8. View in: PubMed

  73. Kim SH, Ikeuchi T, Yu C, Sisodia SS. Regulated hyperaccumulation of presenilin-1 and the "gamma-secretase" complex. Evidence for differential intramembranous processing of transmembrane subatrates. J Biol Chem. 2003 Sep 05; 278(36):33992-4002. View in: PubMed

  74. Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T, Sisodia S, Malinow R. APP processing and synaptic function. Neuron. 2003 Mar 27; 37(6):925-37. View in: PubMed

  75. Ikeuchi T, Sisodia SS. The Notch ligands, Delta1 and Jagged2, are substrates for presenilin-dependent "gamma-secretase" cleavage. J Biol Chem. 2003 Mar 07; 278(10):7751-4. View in: PubMed

  76. Ikeuchi T, Dolios G, Kim SH, Wang R, Sisodia SS. Familial Alzheimer disease-linked presenilin 1 variants enhance production of both Abeta 1-40 and Abeta 1-42 peptides that are only partially sensitive to a potent aspartyl protease transition state inhibitor of "gamma-secretase". J Biol Chem. 2003 Feb 28; 278(9):7010-8. View in: PubMed

  77. Cai D, Leem JY, Greenfield JP, Wang P, Kim BS, Wang R, Lopes KO, Kim SH, Zheng H, Greengard P, Sisodia SS, Thinakaran G, Xu H. Presenilin-1 regulates intracellular trafficking and cell surface delivery of beta-amyloid precursor protein. J Biol Chem. 2003 Jan 31; 278(5):3446-54. View in: PubMed

  78. Lazarov O, Lee M, Peterson DA, Sisodia SS. Evidence that synaptically released beta-amyloid accumulates as extracellular deposits in the hippocampus of transgenic mice. J Neurosci. 2002 Nov 15; 22(22):9785-93. View in: PubMed

  79. Ikeuchi T, Sisodia SS. Cell-free generation of the notch1 intracellular domain (NICD) and APP-CTfgamma: evidence for distinct intramembranous "gamma-secretase" activities. Neuromolecular Med. 2002; 1(1):43-54. View in: PubMed

  80. Mirinics ZK, Calafat J, Udby L, Lovelock J, Kjeldsen L, Rothermund K, Sisodia SS, Borregaard N, Corey SJ. Identification of the presenilins in hematopoietic cells with localization of presenilin 1 to neutrophil and platelet granules. Blood Cells Mol Dis. 2002 Jan-Feb; 28(1):28-38. View in: PubMed

  81. Sisodia SS, St George-Hyslop PH. gamma-Secretase, Notch, Abeta and Alzheimer's disease: where do the presenilins fit in? Nat Rev Neurosci. 2002 Apr; 3(4):281-90. View in: PubMed

  82. Sisodia SS, Annaert W, Kim SH, De Strooper B. Gamma-secretase: never more enigmatic. Trends Neurosci. 2001 Nov; 24(11 Suppl):S2-6. View in: PubMed

  83. Sisodia SS. Biomedicine. A cargo receptor mystery APParently solved? Science. 2002 Feb 01; 295(5556):805-7. View in: PubMed

  84. Borchelt DR, Lee MK, Gonzales V, Slunt HH, Ratovitski T, Jenkins NA, Copeland NG, Price DL, Sisodia SS. Accumulation of proteolytic fragments of mutant presenilin 1 and accelerated amyloid deposition are co-regulated in transgenic mice. Neurobiol Aging. 2002 Mar-Apr; 23(2):171-7. View in: PubMed

  85. Kalback W, Watson MD, Kokjohn TA, Kuo YM, Weiss N, Luehrs DC, Lopez J, Brune D, Sisodia SS, Staufenbiel M, Emmerling M, Roher AE. APP transgenic mice Tg2576 accumulate Abeta peptides that are distinct from the chemically modified and insoluble peptides deposited in Alzheimer's disease senile plaques. Biochemistry. 2002 Jan 22; 41(3):922-8. View in: PubMed

  86. Feng R, Rampon C, Tang YP, Shrom D, Jin J, Kyin M, Sopher B, Miller MW, Ware CB, Martin GM, Kim SH, Langdon RB, Sisodia SS, Tsien JZ. Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron. 2001 Dec 06; 32(5):911-26. View in: PubMed

  87. Kim SH, Creemers JW, Chu S, Thinakaran G, Sisodia SS. Proteolytic processing of familial British dementia-associated BRI variants: evidence for enhanced intracellular accumulation of amyloidogenic peptides. J Biol Chem. 2002 Jan 18; 277(3):1872-7. View in: PubMed

  88. Yu C, Kim SH, Ikeuchi T, Xu H, Gasparini L, Wang R, Sisodia SS. Characterization of a presenilin-mediated amyloid precursor protein carboxyl-terminal fragment gamma. Evidence for distinct mechanisms involved in gamma -secretase processing of the APP and Notch1 transmembrane domains. J Biol Chem. 2001 Nov 23; 276(47):43756-60. View in: PubMed

  89. Kim SH, Leem JY, Lah JJ, Slunt HH, Levey AI, Thinakaran G, Sisodia SS. Multiple effects of aspartate mutant presenilin 1 on the processing and trafficking of amyloid precursor protein. J Biol Chem. 2001 Nov 16; 276(46):43343-50. View in: PubMed

  90. Martys-Zage JL, Kim SH, Berechid B, Bingham SJ, Chu S, Sklar J, Nye J, Sisodia SS. Requirement for presenilin 1 in facilitating lagged 2-mediated endoproteolysis and signaling of notch 1. J Mol Neurosci. 2000 Dec; 15(3):189-204. View in: PubMed

  91. Kim SH, Wang R, Gordon DJ, Bass J, Steiner DF, Thinakaran G, Lynn DG, Meredith SC, Sisodia SS. Familial British dementia: expression and metabolism of BRI. Ann N Y Acad Sci. 2000; 920:93-9. View in: PubMed

  92. Price DL, Wong PC, Markowska AL, Lee MK, Thinakaren G, Cleveland DW, Sisodia SS, Borchelt DR. The value of transgenic models for the study of neurodegenerative diseases. Ann N Y Acad Sci. 2000; 920:179-91. View in: PubMed

  93. Benjannet S, Elagoz A, Wickham L, Mamarbachi M, Munzer JS, Basak A, Lazure C, Cromlish JA, Sisodia S, Checler F, Chrétien M, Seidah NG. Post-translational processing of beta-secretase (beta-amyloid-converting enzyme) and its ectodomain shedding. The pro- and transmembrane/cytosolic domains affect its cellular activity and amyloid-beta production. J Biol Chem. 2001 Apr 06; 276(14):10879-87. View in: PubMed

  94. Sato N, Urano F, Yoon Leem J, Kim SH, Li M, Donoviel D, Bernstein A, Lee AS, Ron D, Veselits ML, Sisodia SS, Thinakaran G. Upregulation of BiP and CHOP by the unfolded-protein response is independent of presenilin expression. Nat Cell Biol. 2000 Dec; 2(12):863-70. View in: PubMed

  95. Takahashi M, Doré S, Ferris CD, Tomita T, Sawa A, Wolosker H, Borchelt DR, Iwatsubo T, Kim SH, Thinakaran G, Sisodia SS, Snyder SH. Amyloid precursor proteins inhibit heme oxygenase activity and augment neurotoxicity in Alzheimer's disease. Neuron. 2000 Nov; 28(2):461-73. View in: PubMed

  96. Heber S, Herms J, Gajic V, Hainfellner J, Aguzzi A, Rülicke T, von Kretzschmar H, von Koch C, Sisodia S, Tremml P, Lipp HP, Wolfer DP, Müller U. Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members. J Neurosci. 2000 Nov 01; 20(21):7951-63. View in: PubMed

  97. Sisodia SS. Neuroscience. An accomplice for gamma-secretase brought into focus. Science. 2000 Sep 29; 289(5488):2296-7. View in: PubMed

  98. Kim SH, Lah JJ, Thinakaran G, Levey A, Sisodia SS. Subcellular localization of presenilins: association with a unique membrane pool in cultured cells. Neurobiol Dis. 2000 Apr; 7(2):99-117. View in: PubMed

  99. Zaman SH, Parent A, Laskey A, Lee MK, Borchelt DR, Sisodia SS, Malinow R. Enhanced synaptic potentiation in transgenic mice expressing presenilin 1 familial Alzheimer's disease mutation is normalized with a benzodiazepine. Neurobiol Dis. 2000 Feb; 7(1):54-63. View in: PubMed

  100. Berechid BE, Thinakaran G, Wong PC, Sisodia SS, Nye JS. Lack of requirement for presenilin1 in Notch1 signaling. Curr Biol. 1999 Dec 16-30; 9(24):1493-6. View in: PubMed

  101. Sisodia SS. Alzheimer's disease: perspectives for the new millennium. J Clin Invest. 1999 Nov; 104(9):1169-70. View in: PubMed

  102. Kim SH, Wang R, Gordon DJ, Bass J, Steiner DF, Lynn DG, Thinakaran G, Meredith SC, Sisodia SS. Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia. Nat Neurosci. 1999 Nov; 2(11):984-8. View in: PubMed

  103. Li XF, Thinakaran G, Sisodia SS, Yu FS. Amyloid precursor-like protein 2 promotes cell migration toward fibronectin and collagen IV. J Biol Chem. 1999 Sep 17; 274(38):27249-56. View in: PubMed

  104. Lamb BT, Bardel KA, Kulnane LS, Anderson JJ, Holtz G, Wagner SL, Sisodia SS, Hoeger EJ. Amyloid production and deposition in mutant amyloid precursor protein and presenilin-1 yeast artificial chromosome transgenic mice. Nat Neurosci. 1999 Aug; 2(8):695-7. View in: PubMed

  105. Sisodia SS, Kim SH, Thinakaran G. Function and dysfunction of the presenilins. Am J Hum Genet. 1999 Jul; 65(1):7-12. View in: PubMed

  106. Kang DE, Soriano S, Frosch MP, Collins T, Naruse S, Sisodia SS, Leibowitz G, Levine F, Koo EH. Presenilin 1 facilitates the constitutive turnover of beta-catenin: differential activity of Alzheimer's disease-linked PS1 mutants in the beta-catenin-signaling pathway. J Neurosci. 1999 Jun 01; 19(11):4229-37. View in: PubMed

  107. Wong PC, Borchelt DR, Lee MK, Pardo CA, Thinakaran G, Martin LJ, Sisodia SS, Price DL. Familial amyotrophic lateral sclerosis and Alzheimer's disease. Transgenic models. Adv Exp Med Biol. 1998; 446:145-59. View in: PubMed

  108. Parent A, Linden DJ, Sisodia SS, Borchelt DR. Synaptic transmission and hippocampal long-term potentiation in transgenic mice expressing FAD-linked presenilin 1. Neurobiol Dis. 1999 Feb; 6(1):56-62. View in: PubMed

  109. Price DL, Tanzi RE, Borchelt DR, Sisodia SS. Alzheimer's disease: genetic studies and transgenic models. Annu Rev Genet. 1998; 32:461-93. View in: PubMed

  110. Greenfield JP, Tsai J, Gouras GK, Hai B, Thinakaran G, Checler F, Sisodia SS, Greengard P, Xu H. Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides. Proc Natl Acad Sci U S A. 1999 Jan 19; 96(2):742-7. View in: PubMed

  111. Naruse S, Thinakaran G, Luo JJ, Kusiak JW, Tomita T, Iwatsubo T, Qian X, Ginty DD, Price DL, Borchelt DR, Wong PC, Sisodia SS. Effects of PS1 deficiency on membrane protein trafficking in neurons. Neuron. 1998 Nov; 21(5):1213-21. View in: PubMed

  112. Buxbaum JD, Thinakaran G, Koliatsos V, O'Callahan J, Slunt HH, Price DL, Sisodia SS. Alzheimer amyloid protein precursor in the rat hippocampus: transport and processing through the perforant path. J Neurosci. 1998 Dec 01; 18(23):9629-37. View in: PubMed

  113. Price DL, Sisodia SS, Borchelt DR. Genetic neurodegenerative diseases: the human illness and transgenic models. Science. 1998 Nov 06; 282(5391):1079-83. View in: PubMed

  114. Borchelt DR, Wong PC, Sisodia SS, Price DL. Transgenic mouse models of Alzheimer's disease and amyotrophic lateral sclerosis. Brain Pathol. 1998 Oct; 8(4):735-57. View in: PubMed

  115. Sisodia SS. Nuclear inclusions in glutamine repeat disorders: are they pernicious, coincidental, or beneficial? Cell. 1998 Oct 02; 95(1):1-4. View in: PubMed

  116. Sisodia SS, Gallagher M. A role for the beta-amyloid precursor protein in memory? Proc Natl Acad Sci U S A. 1998 Oct 13; 95(21):12074-6. View in: PubMed

  117. Borchelt DR, Wong PC, Becher MW, Pardo CA, Lee MK, Xu ZS, Thinakaran G, Jenkins NA, Copeland NG, Sisodia SS, Cleveland DW, Price DL, Hoffman PN. Axonal transport of mutant superoxide dismutase 1 and focal axonal abnormalities in the proximal axons of transgenic mice. Neurobiol Dis. 1998 Jul; 5(1):27-35. View in: PubMed

  118. Tam A, Nouvet FJ, Fujimura-Kamada K, Slunt H, Sisodia SS, Michaelis S. Dual roles for Ste24p in yeast a-factor maturation: NH2-terminal proteolysis and COOH-terminal CAAX processing. J Cell Biol. 1998 Aug 10; 142(3):635-49. View in: PubMed

  119. Price DL, Sisodia SS, Borchelt DR. Alzheimer disease--when and why? Nat Genet. 1998 Aug; 19(4):314-6. View in: PubMed

  120. Price DL, Wong PC, Borchelt DR, Pardo CA, Thinakaran G, Doan AP, Lee MK, Martin LJ, Sisodia SS. Amyotrophic lateral sclerosis and Alzheimer disease. Lessons from model systems. Rev Neurol (Paris). 1997 Sep; 153(8-9):484-95. View in: PubMed

  121. Thinakaran G, Regard JB, Bouton CM, Harris CL, Price DL, Borchelt DR, Sisodia SS. Stable association of presenilin derivatives and absence of presenilin interactions with APP. Neurobiol Dis. 1998 Apr; 4(6):438-53. View in: PubMed

  122. Lyckman AW, Confaloni AM, Thinakaran G, Sisodia SS, Moya KL. Post-translational processing and turnover kinetics of presynaptically targeted amyloid precursor superfamily proteins in the central nervous system. J Biol Chem. 1998 May 01; 273(18):11100-6. View in: PubMed

  123. Xu H, Gouras GK, Greenfield JP, Vincent B, Naslund J, Mazzarelli L, Fried G, Jovanovic JN, Seeger M, Relkin NR, Liao F, Checler F, Buxbaum JD, Chait BT, Thinakaran G, Sisodia SS, Wang R, Greengard P, Gandy S. Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides. Nat Med. 1998 Apr; 4(4):447-51. View in: PubMed

  124. Davis JA, Naruse S, Chen H, Eckman C, Younkin S, Price DL, Borchelt DR, Sisodia SS, Wong PC. An Alzheimer's disease-linked PS1 variant rescues the developmental abnormalities of PS1-deficient embryos. Neuron. 1998 Mar; 20(3):603-9. View in: PubMed

  125. Price DL, Sisodia SS. Mutant genes in familial Alzheimer's disease and transgenic models. Annu Rev Neurosci. 1998; 21:479-505. View in: PubMed

  126. Guo J, Thinakaran G, Guo Y, Sisodia SS, Yu FX. A role for amyloid precursor-like protein 2 in corneal epithelial wound healing. Invest Ophthalmol Vis Sci. 1998 Feb; 39(2):292-300. View in: PubMed

  127. von Koch CS, Zheng H, Chen H, Trumbauer M, Thinakaran G, van der Ploeg LH, Price DL, Sisodia SS. Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiol Aging. 1997 Nov-Dec; 18(6):661-9. View in: PubMed

  128. Bergin A, Kim G, Price DL, Sisodia SS, Lee MK, Rabin BA. Identification and characterization of a mouse homologue of the spinal muscular atrophy-determining gene, survival motor neuron. Gene. 1997 Dec 19; 204(1-2):47-53. View in: PubMed

  129. Borchelt DR, Ratovitski T, van Lare J, Lee MK, Gonzales V, Jenkins NA, Copeland NG, Price DL, Sisodia SS. Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron. 1997 Oct; 19(4):939-45. View in: PubMed

  130. Thinakaran G, Harris CL, Ratovitski T, Davenport F, Slunt HH, Price DL, Borchelt DR, Sisodia SS. Evidence that levels of presenilins (PS1 and PS2) are coordinately regulated by competition for limiting cellular factors. J Biol Chem. 1997 Nov 07; 272(45):28415-22. View in: PubMed

  131. Ratovitski T, Slunt HH, Thinakaran G, Price DL, Sisodia SS, Borchelt DR. Endoproteolytic processing and stabilization of wild-type and mutant presenilin. J Biol Chem. 1997 Sep 26; 272(39):24536-41. View in: PubMed

  132. Lamb BT, Call LM, Slunt HH, Bardel KA, Lawler AM, Eckman CB, Younkin SG, Holtz G, Wagner SL, Price DL, Sisodia SS, Gearhart JD. Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice. Hum Mol Genet. 1997 Sep; 6(9):1535-41. View in: PubMed

  133. Price DL, Borchelt DR, Wong PC, Pardo CA, Thinakaran G, Lee MK, Cleveland DW, Sisodia SS. Neurodegenerative diseases and model systems. Cold Spring Harb Symp Quant Biol. 1996; 61:725-38. View in: PubMed

  134. Lee MK, Borchelt DR, Kim G, Thinakaran G, Slunt HH, Ratovitski T, Martin LJ, Kittur A, Gandy S, Levey AI, Jenkins N, Copeland N, Price DL, Sisodia SS. Hyperaccumulation of FAD-linked presenilin 1 variants in vivo. Nat Med. 1997 Jul; 3(7):756-60. View in: PubMed

  135. Hendriks L, Thinakaran G, Harris CL, De Jonghe C, Martin JJ, Sisodia SS, Van Broeckhoven C. Processing of presenilin 1 in brains of patients with Alzheimer's disease and controls. Neuroreport. 1997 May 06; 8(7):1717-21. View in: PubMed

  136. Wong PC, Zheng H, Chen H, Becher MW, Sirinathsinghji DJ, Trumbauer ME, Chen HY, Price DL, Van der Ploeg LH, Sisodia SS. Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm. Nature. 1997 May 15; 387(6630):288-92. View in: PubMed

  137. Seeger M, Nordstedt C, Petanceska S, Kovacs DM, Gouras GK, Hahne S, Fraser P, Levesque L, Czernik AJ, George-Hyslop PS, Sisodia SS, Thinakaran G, Tanzi RE, Greengard P, Gandy S. Evidence for phosphorylation and oligomeric assembly of presenilin 1. Proc Natl Acad Sci U S A. 1997 May 13; 94(10):5090-4. View in: PubMed

  138. Borchelt DR, Davis J, Fischer M, Lee MK, Slunt HH, Ratovitsky T, Regard J, Copeland NG, Jenkins NA, Sisodia SS, Price DL. A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet Anal. 1996 Dec; 13(6):159-63. View in: PubMed

  139. Li HL, Roch JM, Sundsmo M, Otero D, Sisodia S, Thomas R, Saitoh T. Defective neurite extension is caused by a mutation in amyloid beta/A4 (A beta) protein precursor found in familial Alzheimer's disease. J Neurobiol. 1997 May; 32(5):469-80. View in: PubMed

  140. Xu H, Sweeney D, Wang R, Thinakaran G, Lo AC, Sisodia SS, Greengard P, Gandy S. Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation. Proc Natl Acad Sci U S A. 1997 Apr 15; 94(8):3748-52. View in: PubMed

  141. Bruijn LI, Becher MW, Lee MK, Anderson KL, Jenkins NA, Copeland NG, Sisodia SS, Rothstein JD, Borchelt DR, Price DL, Cleveland DW. ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron. 1997 Feb; 18(2):327-38. View in: PubMed

  142. Zhao B, Chrest FJ, Horton WE, Sisodia SS, Kusiak JW. Expression of mutant amyloid precursor proteins induces apoptosis in PC12 cells. J Neurosci Res. 1997 Feb 01; 47(3):253-63. View in: PubMed

  143. Walter J, Capell A, Hung AY, Langen H, Schnölzer M, Thinakaran G, Sisodia SS, Selkoe DJ, Haass C. Ectodomain phosphorylation of beta-amyloid precursor protein at two distinct cellular locations. J Biol Chem. 1997 Jan 17; 272(3):1896-903. View in: PubMed

  144. Marquez-Sterling NR, Lo AC, Sisodia SS, Koo EH. Trafficking of cell-surface beta-amyloid precursor protein: evidence that a sorting intermediate participates in synaptic vesicle recycling. J Neurosci. 1997 Jan 01; 17(1):140-51. View in: PubMed

  145. Levitan D, Doyle TG, Brousseau D, Lee MK, Thinakaran G, Slunt HH, Sisodia SS, Greenwald I. Assessment of normal and mutant human presenilin function in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1996 Dec 10; 93(25):14940-4. View in: PubMed

  146. Price DL, Becher MW, Wong PC, Borchelt DR, Lee MK, Sisodia SS. Inherited neurodegenerative diseases and transgenic models. Brain Pathol. 1996 Oct; 6(4):467-80. View in: PubMed

  147. Wang R, Sweeney D, Gandy SE, Sisodia SS. The profile of soluble amyloid beta protein in cultured cell media. Detection and quantification of amyloid beta protein and variants by immunoprecipitation-mass spectrometry. J Biol Chem. 1996 Dec 13; 271(50):31894-902. View in: PubMed

  148. Doan A, Thinakaran G, Borchelt DR, Slunt HH, Ratovitsky T, Podlisny M, Selkoe DJ, Seeger M, Gandy SE, Price DL, Sisodia SS. Protein topology of presenilin 1. Neuron. 1996 Nov; 17(5):1023-30. View in: PubMed

  149. Borchelt DR, Thinakaran G, Eckman CB, Lee MK, Davenport F, Ratovitsky T, Prada CM, Kim G, Seekins S, Yager D, Slunt HH, Wang R, Seeger M, Levey AI, Gandy SE, Copeland NG, Jenkins NA, Price DL, Younkin SG, Sisodia SS. Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron. 1996 Nov; 17(5):1005-13. View in: PubMed

  150. Lee MK, Borchelt DR, Wong PC, Sisodia SS, Price DL. Transgenic models of neurodegenerative diseases. Curr Opin Neurobiol. 1996 Oct; 6(5):651-60. View in: PubMed

  151. Lee MK, Slunt HH, Martin LJ, Thinakaran G, Kim G, Gandy SE, Seeger M, Koo E, Price DL, Sisodia SS. Expression of presenilin 1 and 2 (PS1 and PS2) in human and murine tissues. J Neurosci. 1996 Dec 01; 16(23):7513-25. View in: PubMed

  152. Bressler SL, Gray MD, Sopher BL, Hu Q, Hearn MG, Pham DG, Dinulos MB, Fukuchi K, Sisodia SS, Miller MA, Disteche CM, Martin GM. cDNA cloning and chromosome mapping of the human Fe65 gene: interaction of the conserved cytoplasmic domains of the human beta-amyloid precursor protein and its homologues with the mouse Fe65 protein. Hum Mol Genet. 1996 Oct; 5(10):1589-98. View in: PubMed

  153. Price DL, Koliatsos VE, Wong PC, Pardo CA, Borchelt DR, Lee MK, Cleveland DW, Griffin JW, Hoffman PN, Cork LC, Sisodia SS. Motor neuron disease and model systems: aetiologies, mechanisms and therapies. Ciba Found Symp. 1996; 196:3-13; discussion 13-7. View in: PubMed

  154. Crain BJ, Hu W, Sze CI, Slunt HH, Koo EH, Price DL, Thinakaran G, Sisodia SS. Expression and distribution of amyloid precursor protein-like protein-2 in Alzheimer's disease and in normal brain. Am J Pathol. 1996 Oct; 149(4):1087-95. View in: PubMed

  155. Cleveland DW, Bruijn LI, Wong PC, Marszalek JR, Vechio JD, Lee MK, Xu XS, Borchelt DR, Sisodia SS, Price DL. Mechanisms of selective motor neuron death in transgenic mouse models of motor neuron disease. Neurology. 1996 Oct; 47(4 Suppl 2):S54-61; discussion S61-2. View in: PubMed

  156. Borchelt DR, Sisodia SS. Loss of functional prion protein: a role in prion disorders? Chem Biol. 1996 Aug; 3(8):619-21. View in: PubMed

  157. Calingasan NY, Gandy SE, Baker H, Sheu KF, Smith JD, Lamb BT, Gearhart JD, Buxbaum JD, Harper C, Selkoe DJ, Price DL, Sisodia SS, Gibson GE. Novel neuritic clusters with accumulations of amyloid precursor protein and amyloid precursor-like protein 2 immunoreactivity in brain regions damaged by thiamine deficiency. Am J Pathol. 1996 Sep; 149(3):1063-71. View in: PubMed

  158. Thinakaran G, Borchelt DR, Lee MK, Slunt HH, Spitzer L, Kim G, Ratovitsky T, Davenport F, Nordstedt C, Seeger M, Hardy J, Levey AI, Gandy SE, Jenkins NA, Copeland NG, Price DL, Sisodia SS. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron. 1996 Jul; 17(1):181-90. View in: PubMed

  159. Sisodia SS, Thinakaran G, Slunt HH, Kitt CA, Von Koch CS, Reed RR, Zheng H, Price DL. Studies on the metabolism and biological function of APLP2. Ann N Y Acad Sci. 1996 Jan 17; 777:77-81. View in: PubMed

  160. Zheng H, Jiang M, Trumbauer ME, Hopkins R, Sirinathsinghji DJ, Stevens KA, Conner MW, Slunt HH, Sisodia SS, Chen HY, Van der Ploeg LH. Mice deficient for the amyloid precursor protein gene. Ann N Y Acad Sci. 1996 Jan 17; 777:421-6. View in: PubMed

  161. Thinakaran G, Teplow DB, Siman R, Greenberg B, Sisodia SS. Metabolism of the "Swedish" amyloid precursor protein variant in neuro2a (N2a) cells. Evidence that cleavage at the "beta-secretase" site occurs in the golgi apparatus. J Biol Chem. 1996 Apr 19; 271(16):9390-7. View in: PubMed

  162. Sisodia SS, Koo EH, Hoffman PN, Perry G, Price DL. Identification and transport of full-length amyloid precursor proteins in rat peripheral nervous system. J Neurosci. 1993 Jul; 13(7):3136-42. View in: PubMed

  163. da Cruz e Silva OA, Iverfeldt K, Oltersdorf T, Sinha S, Lieberburg I, Ramabhadran TV, Suzuki T, Sisodia SS, Gandy S, Greengard P. Regulated cleavage of Alzheimer beta-amyloid precursor protein in the absence of the cytoplasmic tail. Neuroscience. 1993 Dec; 57(4):873-7. View in: PubMed

  164. Slunt HH, Thinakaran G, Von Koch C, Lo AC, Tanzi RE, Sisodia SS. Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid precursor protein (APP). J Biol Chem. 1994 Jan 28; 269(4):2637-44. View in: PubMed

  165. Wasco W, Gurubhagavatula S, Paradis MD, Romano DM, Sisodia SS, Hyman BT, Neve RL, Tanzi RE. Isolation and characterization of APLP2 encoding a homologue of the Alzheimer's associated amyloid beta protein precursor. Nat Genet. 1993 Sep; 5(1):95-100. View in: PubMed

  166. Lamb BT, Sisodia SS, Lawler AM, Slunt HH, Kitt CA, Kearns WG, Pearson PL, Price DL, Gearhart JD. Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice [corrected]. Nat Genet. 1993 Sep; 5(1):22-30. View in: PubMed

  167. Price DL, Sisodia SS. Cellular and molecular biology of Alzheimer's disease and animal models. Annu Rev Med. 1994; 45:435-46. View in: PubMed

  168. Price DL, Borchelt DR, Sisodia SS. Alzheimer disease and the prion disorders amyloid beta-protein and prion protein amyloidoses. Proc Natl Acad Sci U S A. 1993 Jul 15; 90(14):6381-4. View in: PubMed

  169. Thinakaran G, Sisodia SS. Amyloid precursor-like protein 2 (APLP2) is modified by the addition of chondroitin sulfate glycosaminoglycan at a single site. J Biol Chem. 1994 Sep 02; 269(35):22099-104. View in: PubMed

  170. Borchelt DR, Lee MK, Slunt HS, Guarnieri M, Xu ZS, Wong PC, Brown RH, Price DL, Sisodia SS, Cleveland DW. Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc Natl Acad Sci U S A. 1994 Aug 16; 91(17):8292-6. View in: PubMed

  171. Lo AC, Haass C, Wagner SL, Teplow DB, Sisodia SS. Metabolism of the "Swedish" amyloid precursor protein variant in Madin-Darby canine kidney cells. J Biol Chem. 1994 Dec 09; 269(49):30966-73. View in: PubMed

  172. Sisodia SS, Price DL. Role of the beta-amyloid protein in Alzheimer's disease. FASEB J. 1995 Mar; 9(5):366-70. View in: PubMed

  173. Lai A, Sisodia SS, Trowbridge IS. Characterization of sorting signals in the beta-amyloid precursor protein cytoplasmic domain. J Biol Chem. 1995 Feb 24; 270(8):3565-73. View in: PubMed

  174. Pardo CA, Xu Z, Borchelt DR, Price DL, Sisodia SS, Cleveland DW. Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons. Proc Natl Acad Sci U S A. 1995 Feb 14; 92(4):954-8. View in: PubMed

  175. Borchelt DR, Guarnieri M, Wong PC, Lee MK, Slunt HS, Xu ZS, Sisodia SS, Price DL, Cleveland DW. Superoxide dismutase 1 subunits with mutations linked to familial amyotrophic lateral sclerosis do not affect wild-type subunit function. J Biol Chem. 1995 Feb 17; 270(7):3234-8. View in: PubMed

  176. Van Nostrand WE, Schmaier AH, Neiditch BR, Siegel RS, Raschke WC, Sisodia SS, Wagner SL. Expression, purification, and characterization of the Kunitz-type proteinase inhibitor domain of the amyloid beta-protein precursor-like protein-2. Biochim Biophys Acta. 1994 Dec 14; 1209(2):165-70. View in: PubMed

  177. Lo AC, Thinakaran G, Slunt HH, Sisodia SS. Metabolism of the amyloid precursor-like protein 2 in MDCK cells. Polarized trafficking occurs independent of the chondroitin sulfate glycosaminoglycan chain. J Biol Chem. 1995 May 26; 270(21):12641-5. View in: PubMed

  178. Zhao B, Sisodia SS, Kusiak JW. Altered processing of a mutant amyloid precursor protein in neuronal and endothelial cells. J Neurosci Res. 1995 Feb 01; 40(2):261-8. View in: PubMed

  179. Sisodia SS, Martin LJ, Walker LC, Borchelt DR, Price DL. Cellular and molecular biology of Alzheimer's disease and animal models. Neuroimaging Clin N Am. 1995 Feb; 5(1):59-68. View in: PubMed

  180. Rabizadeh S, Gralla EB, Borchelt DR, Gwinn R, Valentine JS, Sisodia S, Wong P, Lee M, Hahn H, Bredesen DE. Mutations associated with amyotrophic lateral sclerosis convert superoxide dismutase from an antiapoptotic gene to a proapoptotic gene: studies in yeast and neural cells. Proc Natl Acad Sci U S A. 1995 Mar 28; 92(7):3024-8. View in: PubMed

  181. Sisodia SS. Cellular and molecular genetic approaches in Alzheimer's disease. Neurobiol Aging. 1994; 15 Suppl 2:S135-7. View in: PubMed

  182. Thinakaran G, Slunt HH, Sisodia SS. Novel regulation of chondroitin sulfate glycosaminoglycan modification of amyloid precursor protein and its homologue, APLP2. J Biol Chem. 1995 Jul 14; 270(28):16522-5. View in: PubMed

  183. Wong PC, Pardo CA, Borchelt DR, Lee MK, Copeland NG, Jenkins NA, Sisodia SS, Cleveland DW, Price DL. An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron. 1995 Jun; 14(6):1105-16. View in: PubMed

  184. von Koch CS, Lahiri DK, Mammen AL, Copeland NG, Gilbert DJ, Jenkins NA, Sisodia S. The mouse APLP2 gene. Chromosomal localization and promoter characterization. J Biol Chem. 1995 Oct 27; 270(43):25475-80. View in: PubMed

  185. Price DL, Sisodia SS, Gandy SE. Amyloid beta amyloidosis in Alzheimer's disease. Curr Opin Neurol. 1995 Aug; 8(4):268-74. View in: PubMed

  186. Reeves RH, Irving NG, Moran TH, Wohn A, Kitt C, Sisodia SS, Schmidt C, Bronson RT, Davisson MT. A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet. 1995 Oct; 11(2):177-84. View in: PubMed

  187. Borchelt DR, Koliatsos VE, Guarnieri M, Pardo CA, Sisodia SS, Price DL. Rapid anterograde axonal transport of the cellular prion glycoprotein in the peripheral and central nervous systems. J Biol Chem. 1994 May 20; 269(20):14711-4. View in: PubMed

  188. Sisodia SS, Sollner-Webb B, Cleveland DW. Specificity of RNA maturation pathways: RNAs transcribed by RNA polymerase III are not substrates for splicing or polyadenylation. Mol Cell Biol. 1987 Oct; 7(10):3602-12. View in: PubMed

  189. Gabriel A, Sisodia SS, Cleveland DW. Evidence of discontinuous transcription in the trypanosomatid Crithidia fasciculata. J Biol Chem. 1987 Nov 25; 262(33):16192-9. View in: PubMed

  190. Gay DA, Sisodia SS, Cleveland DW. Autoregulatory control of beta-tubulin mRNA stability is linked to translation elongation. Proc Natl Acad Sci U S A. 1989 Aug; 86(15):5763-7. View in: PubMed

  191. Price DL, Sisodia SS, Koo EH, Muma NA, Kitt CA, Walker LC, Martin LJ, Troncoso JC, Griffin JW, Hoffman PN, et al. Neuronal disorders: studies of animal models and human diseases. Toxicol Pathol. 1990; 18(1 Pt 2):128-37. View in: PubMed

  192. Koo EH, Sisodia SS, Cork LC, Unterbeck A, Bayney RM, Price DL. Differential expression of amyloid precursor protein mRNAs in cases of Alzheimer's disease and in aged nonhuman primates. Neuron. 1990 Jan; 4(1):97-104. View in: PubMed

  193. Price DL, Koo EH, Sisodia SS, Martin LJ, Koliatsos VE, Muma NA, Walker LC, Cork LC. Neuronal responses to injury and aging: lessons from animal models. Prog Brain Res. 1990; 86:297-308. View in: PubMed

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