Physiological Functions of Presenilins; Beyond gamma-Secretase.

Abstract

Presenilin (PS) was identified in screens for mutations causing the early onset forms of familial Alzheimer's disease (FAD) in 1995. As catalytic units of the gamma-secretase complex, presenilins participate in the processing of amyloid beta protein (Abeta), the main component of deposits in brain of patients with AD. The more than 90 substrates of gamma-secretase isolated so far demonstrate its contribution to wide range of cellular processes and signaling events. However, recent findings have revealed numerous gamma-secretase-independent presenilin functions, including involvement in calcium homeostasis, endoplasmic reticulum (ER) stress and autophagy. This mini-review attempts to summarize the multiple physiological and pathological functions of presenilin.