Modifications and Trafficking of APP in the Pathogenesis of Alzheimer’s Disease

Frontiers in Molecular Neuroscience

Gongying Li¹  Xin Wang³  Xuan Zhou³  Yili Wu⁴  Weihong Song⁴  Yun Zhang⁴ 

[1] Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical UniversityJining, China;Department of Psychiatry, Jining Medical UniversityJining, China;Shandong Key Laboratory of Behavioral Medicine, Jining Medical UniversityJining, China;Townsend Family Laboratories, Department of Psychiatry, The University of British ColumbiaVancouver, BC, Canada;

关键词: Alzheimer’s disease;    APP;    Aβ;    post-translational modifications;    trafficking;   

DOI  :  10.3389/fnmol.2017.00294

来源: DOAJ

【 摘 要 】

Alzheimer’s disease (AD), the most common neurodegenerative disorder, is the leading cause of dementia. Neuritic plaque, one of the major characteristics of AD neuropathology, mainly consists of amyloid β (Aβ) protein. Aβ is derived from amyloid precursor protein (APP) by sequential cleavages of β- and γ-secretase. Although APP upregulation can promote AD pathogenesis by facilitating Aβ production, growing evidence indicates that aberrant post-translational modifications and trafficking of APP play a pivotal role in AD pathogenesis by dysregulating APP processing and Aβ generation. In this report, we reviewed the current knowledge of APP modifications and trafficking as well as their role in APP processing. More importantly, we discussed the effect of aberrant APP modifications and trafficking on Aβ generation and the underlying mechanisms, which may provide novel strategies for drug development in AD.

【 授权许可】

Unknown