Presenilin and Alzheimer's disease: calcium signaling pathway / 中华行为医学与脑科学杂志

ABSTRACT

Presenilin (PS) is the main pathogenic gene of familial Alzheimer's disease(AD). Mutations of PS gene can promote the processing of amyloid precursor protein (APP) into a toxic form of amyloid beta protein (Aβ), which plays an important role in the pathogenesis of AD.However, the current targeted therapy for Aβ has not yet produced a good effect on AD, suggesting the existence of additional pathogenic mechanisms.In recent years, the abnormal calcium homeostasis and its pathological role in AD have attracted people's attention.The calcium signaling pathway is regulated by presenilin.And the calcium regulation of PS gene mutant neurons is impaired, resulting in reduced ability to deal with oxidative stress, which leads to cell death and promotes the occurrence of AD.In addition, damage to neuronal autophagy induced by PS gene mutations also depends on the ability to partially deplete endoplasmic reticulum calcium content.Recent studies have shown that abnormal Ca 2+ homeostasis caused by PS gene mutations can lead to impaired mitochondrial metabolism and defects in brain network activity.This review will focus on the calcium signaling pathway, and explore the pathogenesis of presenilin in AD through the regulation of calcium signals from the perspectives of impaired autophagy, endoplasmic reticulum stress, mitochondrial dysfunction, apoptosis and defects in brain network activity, so as to provide ideas for the etiology of AD and the discovery of drug targets.