Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer”s disease
Neurofibrillary tangles (NFTs), composed of truncated and hyperphosphorylated tau, are a common feature of numerous aging related neurodegenerative diseases, including Alzheimer”s disease (AD).However, the molecular mechanisms mediating tau truncation and aggregation during aging remain elusive.Here we show that asparagine endopeptidase (AEP), a lysosomal cysteine proteinase, is activated during aging and proteolytically degrades tau, abolishes its microtubule assembly function, induces tau aggregation and triggers neurodegeneration.AEP is upregulated and active during aging and is activated in human AD brain and tau P301S-transgenic mice with synaptic pathology and behavioral impairments, leading to tau truncation in NFTs.
Zhentao Zhang
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060
国内会议
武汉
英文
99-99
2015-07-03（万方平台首次上网日期，不代表论文的发表时间）