Presenilins (PSs) were first identified in early 1990s as multipass transmembrane proteins those mutations causing familial early-onset forms of Alzheimer disease in which symptoms usually develop between a person’s early 40s and mid-50s. Alzheimer’s disease (AD), as the most common form of dementia, is a major public health problem in the world especially in developed country. Presenilins, the core units of the γ -secretase complex, participate in the process of amyloid beta protein (Aβ) that plays central role in the pathogenesis of AD. However, there are numerous pieces of evidence that PS mutations have several γ -secretase-independent effects.
Presenilins and γ-Secretase Assembly
PSs are highly conserved transmembrane proteins with aspartyl protease activity, characterized by nine helical transmembrane domains (TMD). In mammals, two homologs are present: PS1 and PS2. The homology between them is about 67%. PSs are mostly localized in the ER, Golgi, and in...
- Avrahami L, Farfara D, Shaham-Kol M, Vassar R, Frenkel D, Eldar-Finkelman H. Inhibition of glycogen synthase kinase-3 ameliorates beta-amyloid pathology and restores lysosomal acidification and mammalian target of rapamycin activity in the Alzheimer disease mouse model. J Biol Chem. 2013;288(2):1295–306.CrossRefPubMedGoogle Scholar