Jan 8, 2015

The γ-secretase complex: from structure to function

Frontiers in Cellular Neuroscience
Xian ZhangYun-wu Zhang

Abstract

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.

Mentioned in this Paper

Presenilins
APP protein, human
Extracellular
Amyloid Beta Precursor Protein Measurement
Brain
Cytokinesis of the Fertilized Ovum
Integral to Membrane
Alzheimer's Disease
NCSTN gene
Amyloid Deposition

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