中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (10): 2215-2217.doi: 10.4103/1673-5374.335818

• 观点:退行性病与再生 • 上一篇    下一篇

氨肽酶A和二肽基肽酶4:阿尔茨海默病的致病二重奏?

  

  • 出版日期:2022-10-15 发布日期:2022-03-16

Aminopeptidase A and dipeptidyl peptidase 4: a pathogenic duo in Alzheimer’s disease?

Frédéric Checler, Audrey Valverde   

  1. Université Côte d’Azur, INSERM, CNRS, IPMC, team labelled “Laboratory of Excellence (LABEX) DistAlz”, Valbonne, France
  • Online:2022-10-15 Published:2022-03-16
  • Contact: Frédéric Checler, PhD, checler@ipmc.cnrs.fr.
  • Supported by:
    Initial works were supported through the LABEX (excellence laboratory, program investment for the future) DISTALZ (Development of innovative strategies for a transdisciplinary approach to Alzheimer’s disease), the Hospital University Federation (FHU) OncoAge and the Fondation Plan Alzheimer.

摘要: https://orcid.org/0000-0003-2098-1750 (Frédéric Checler)

Abstract: The etiology of Alzheimer’s disease is far from being completely understood. Genetic approaches have helped in this matter and have greatly supported the view that the β-amyloid precursor protein (βAPP) could be at the center of gravity of the pathology. Thus, mutations responsible for autosomal dominant aggressive forms of Alzheimer’s disease (AD) are all harbored by either βAPP itself or by its cleaving enzyme presenilins 1/2 referred to as γ-secretase. It was therefore convincing to note that fully independent gene products harboring AD-linked mutations, all concur to modulate βAPP proteolytic processing. These genetic clues combined with a bulk of anatomical observations and cellular manipulations pointed to the role of amyloid-β (Aβ), the main biochemical component of senile plaques that accumulate at late stages of AD. Unfortunately, a series of clinical trials designed to either abolish Aβ production or neutralize it once produced have consistently failed (Checler et al., 2021). It remains that the genetic arguments are strong and that a key role of βAPP proteolytic maturation remains of actuality. One way to reconcile genetic evidence and clinical trials failure could be to envision that additional βAPP-derived products could contribute to AD etiology. A close evaluation of biogenesis and toxicity of such pathogenic βAPP-derived products, distinct from genuine Aβ could help to better understand AD etiology.