Recent developments of small molecule γ-secretase modulators for Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is the most common form of progressive neurodegenerative disorder, marked by memory loss and a decline in cognitive function. The major hallmarks of AD are the presence of intracellular neurofibrillary tau tangles (NFTs) composed of hyperphosphorylated tau proteins and extracellular plaques composed of amyloid beta peptides (Aβ). The amyloid (Aβ) cascade hypothesis proposes that the AD pathogenesis is initiated by the accumulation of Aβ peptides in the parenchyma of the brain. An aspartyl intramembranal protease called γ-secretase is responsible for the production of Aβ by the cleavage of the amyloid precursor protein (APP). Clinical studies of γ-secretase inhibitors (GSIs) for AD failed due to the lack of substrate specificity. Therefore, γ-secretase modulators (G

SUBMITTER: Mekala S 

PROVIDER: S-EPMC7513388 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature