PlumX Metrics
Embed PlumX Metrics

Amphiphysin i cleavage by asparagine endopeptidase leads to tau hyperphosphorylation and synaptic dysfunction

eLife, ISSN: 2050-084X, Vol: 10
2021
  • 12
    Citations
  • 0
    Usage
  • 10
    Captures
  • 1
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Most Recent News

Amphiphysin I cleavage by asparagine endopeptidase leads to tau hyperphosphorylation and synaptic dysfunction.

Elife. 2021 May 21;10 Authors: Zhang X, Zou L, Meng L, Xiong M, Pan L, Chen G, Zheng Y, Xiong J, Wang Z, Duong DM, Zhang Z, Cao X, Wang T, Tang L, Ye K, Zhang Z PubMed: 34018922 Submit Comment

Article Description

Neurofibrillary tangles composed of hyperphosphorylated tau and synaptic dysfunction are characteristics of Alzheimer’s disease (AD). However, the underlying molecular mechanisms remain poorly understood. Here, we identified Amphiphysin I mediates both tau phosphorylation and synaptic dysfunction in AD. Amphiphysin I is cleaved by a cysteine proteinase asparagine endopeptidase (AEP) at N278 in the brains of AD patients. The amount of AEP-generated N-terminal fragment of Amphiphysin I (1-278) is increased with aging. Amphiphysin I (1-278) inhibits clathrin-mediated endocytosis and induces synaptic dysfunction. Furthermore, Amphiphysin I (1-278) binds p35 and promotes its transition to p25, thus activates CDK5 and enhances tau hyperphosphorylation. Overexpression of Amphiphysin I (1-278) in the hippocampus of Tau P301S mice induces synaptic dysfunction, tau hyperphosphorylation, and cognitive deficits. However, overexpression of the N278A mutant Amphiphysin I, which resists the AEP-mediated cleavage, alleviates the pathological and behavioral defects. These findings suggest a mechanism of tau hyperphosphorylation and synaptic dysfunction in AD.

Bibliographic Details

Zhang, Xingyu; Zou, Li; Meng, Lanxia; Xiong, Min; Pan, Lina; Chen, Guiqin; Zheng, Yongfa; Xiong, Jing; Wang, Zhihao; Duong, Duc M; Zhang, Zhaohui; Cao, Xuebing; Wang, Tao; Tang, Li; Ye, Keqiang; Zhang, Zhentao

eLife Sciences Publications, Ltd

Neuroscience; Biochemistry, Genetics and Molecular Biology; Immunology and Microbiology

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know