δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities

• 作者: Keqiang Ye Ye Tian Zhentao Zhang
• 来源期刊: 转化神经变性病(英文)
• 学科: 医学
• 关键词: AEP Alzheimer’s DISEASE Parkinson’s DISEASE C/EBPΒ TrkB TDP-43
• 年，卷（期）: zhsjbxbyw_2020,（1）
• 页码范围: 1-9
• 页数: 9页
• 分类号: R74

摘要

Mammalian asparagine endopeptidase(AEP)is a cysteine protease that cleaves its protein substrates on the Cterminal side of asparagine residues.Converging lines of evidence indicate that AEP may be involved in the pathogenesis of several neurological diseases,including Alzheimer’s disease,Parkinson’s disease,and frontotemporal dementia.AEP is activated in the aging brain,cleaves amyloid precursor protein(APP)and promotes the production of amyloid-β(Aβ).We renamed AEP to δ-secretase to emphasize its role in APP fragmentation and Aβ production.AEP also cleaves other substrates,such as tau,α-synuclein,SET,and TAR DNA-binding protein 43,generating neurotoxic fragments and disturbing their physiological functions.The activity of δ-secretase is tightly regulated at both the transcriptional and posttranslational levels.Here,we review the recent advances in the role of δ-secretase in neurodegenerative diseases,with a focus on its biochemical properties and the transcriptional and posttranslational regulation of its activity,and discuss the clinical implications of δ-secretase as a diagnostic biomarker and therapeutic target for neurodegenerative diseases.