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P2‐272: Reconstructing the gamma‐secretase complex using the multibac baculovirus system for expression of heterologous multi‐protein complexes
Author(s) -
Verdile Giuseppe,
Krishnaswamy Sudarsan,
Berger Imre,
Groth David,
Fraser Paul,
Martins Ralph N.
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.1322
Subject(s) - biology , heterologous , transfection , expression vector , microbiology and biotechnology , heterologous expression , vector (molecular biology) , gene , cloning (programming) , viral vector , expression cassette , cloning vector , recombinant dna , genetics , computer science , programming language
autolysosomes acidification and cathepsin activation. Neurons in mice hypomorphic for PS1 or conditionally depleted of PS1 display similar abnormalities. PS1 mutations causing early-onset AD produce a similar lysosomal/autophagy phenotype and partial loss of autophagy function as shown in fibroblasts from patients with familial AD. Conclusions: PS1 is essential for lysosome acidification and proteolysis during autophagy. Disruption of autophagy function by PS1 mutations promotes accumulation of pathogenic proteins and neuronal death in AD underscoring the significance of lysosomal system dysfunction in AD pathogenesis.