Current Alzheimer Research

Prof. Debomoy K. Lahiri  
Department of Psychiatry, Indiana University School of Medicine
Neuroscience Research Center
Indianapolis, IN 46202


The Catalytic Core of γ-Secretase: Presenilin Revisited

Author(s): Harald Steiner

Affiliation: Adolf-Butenandt-Institute,Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Schillerstr. 44, Ludwig-Maximilians-University, 80336 Munich,Germany.


Mutations in the presenilin 1 (PS1) gene are the major cause of familial Alzheimers disease (AD). They effect an increased production of the highly neurotoxic 42 amino acid variant of the amyloid-β peptide (Aβ), which is believed to initiate the disease. Aβ is the product of two consecutive cleavages of the β-amyloid precursor protein (APP) by two proteases, β-secretase and γ-secretase. The latter enzyme has been identified as an intramembrane-cleaving multiprotein complex that apart from APP cleaves a large number of other type I transmembrane proteins. PS1 and its homologue PS2 are essential for γ-secretase cleavage and more than a decade after their discovery it is now firmly established that they function as catalytic subunits of γ-secretase. This review recapitulates the findings that led to this conclusion as well as the further progress made on the function of PS as γ-secretase since then.

Keywords: Alzheimer's disease, Amyloid β-peptide, presenilin, γ-secretase

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Article Details

Page: [147 - 157]
Pages: 11
DOI: 10.2174/156720508783954677