AUTHOR=Zhang Xian , Li Yanfang , Xu Huaxi , Zhang Yun-Wu 

TITLE=The γ-secretase complex: from structure to function

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=8

YEAR=2014

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2014.00427

DOI=10.3389/fncel.2014.00427

ISSN=1662-5102

ABSTRACT=<p>One of the most critical pathological features of Alzheimer’s disease (AD) is the accumulation of β-amyloid (Aβ) peptides that form extracellular senile plaques in the brain. Aβ is derived from β-amyloid precursor protein (APP) through sequential cleavage by β- and γ-secretases. γ-secretase is a high molecular weight complex minimally composed of four components: presenilins (PS), nicastrin, anterior pharynx defective 1 (APH-1), and presenilin enhancer 2 (PEN-2). In addition to APP, γ-secretase also cleaves many other type I transmembrane (TM) protein substrates. As a crucial enzyme for Aβ production, γ-secretase is an appealing therapeutic target for AD. Here, we summarize current knowledge on the structure and function of γ-secretase, as well as recent progress in developing γ-secretase targeting drugs for AD treatment.</p>