1. Academic Validation
  2. CPNE7 Regulates Amyloidogenesis Through CAP1-Dependent ADAM10 Translation

CPNE7 Regulates Amyloidogenesis Through CAP1-Dependent ADAM10 Translation

  • J Neurochem. 2025 Mar;169(3):e70026. doi: 10.1111/jnc.70026.
Jie Yang 1 2 Ya-Lan Pu 3 4 Qiu-Lin Pan 3 Lu Wang 3 Chen-Lu Li 3 Xiao-Yong Xie 3 Xue Chen 3 Xiao-Yun Li 3 Ding-Qun Bai 1 Bing-Lin Zhu 5 Guo-Jun Chen 3
Affiliations

Affiliations

  • 1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of Neurological Rehabilitation, Affiliated Sichuan Provincial Rehabilitation Hospital of Chengdu University of TCM, Chengdu, China.
  • 3 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, China.
  • 4 Department of Neurology, Langzhong People's Hospital, Nanchong, China.
  • 5 Jinfeng Laboratory, Chongqing, China.
Abstract

The accumulation of amyloid plaques is a pathological hallmark of Alzheimer's disease (AD), in which ADAM10, the α-secretase that catalyzes APP and facilitates the non-amyloidogenesis pathway, plays an important role. We have previously reported that the expression of copine-7 (Cpne7) in the hippocampus of APP/PS1 mice is significantly upregulated by nicotine, whereas the potential role of CPNE7 in AD remains largely unknown. Here, we report that CPNE7 protein levels are significantly decreased in APP/PS1 mice and HEK293 cells stably expressing full-length APP. CPNE7 is shown to reduce Aβ levels by favoring ADAM10 activity, and the elevated ADAM10 protein by CPNE7 involves a translational mechanism. Further transcriptome profiling reveals that CPNE7 differentially regulates genes associated with neuronal function. Among these, cyclase-associated actin Cytoskeleton regulatory protein 1 (CAP1) is identified as a target gene of CPNE7, which controls ADAM10 translation through binding to the 5' untranslated region (5'UTR). Collectively, the CPNE7-CAP1 axis could be critical in the amyloidogenic pathway by regulating ADAM10 translation, in which the RNA binding activity of CAP1 is highlighted.

Keywords

ADAM10; Alzheimer's disease (AD); CAP1; CPNE7; RNA‐binding protein (RBP).

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