2. Academic Validation
  3. CEND1 deficiency induces mitochondrial dysfunction and cognitive impairment in Alzheimer's disease

CEND1 deficiency induces mitochondrial dysfunction and cognitive impairment in Alzheimer's disease

  • Cell Death Differ. 2022 Jun 22. doi: 10.1038/s41418-022-01027-7.
Wenting Xie  # 1,  Dong Guo  # 1,  Jieyin Li  # 1,  Lei Yue 2,  Qi Kang 1,  Guimiao Chen 1,  Tingwen Zhou 1,  Han Wang 1,  Kai Zhuang 1,  Lige Leng 1,  Huifang Li 1,  Zhenyi Chen 3,  Weiwei Gao 4,  Jie Zhang 5 6 7
Affiliations

Affiliations

  • 1 Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian, 361005, China.
  • 2 Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou, Fujian, 350004, China.
  • 3 Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, 361005, China.
  • 4 Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou, Fujian, 350004, China. gaoww@fjmu.edu.cn.
  • 5 Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian, 361005, China. jiezhang@xmu.edu.cn.
  • 6 Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou, Fujian, 350004, China. jiezhang@xmu.edu.cn.
  • 7 Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, 361005, China. jiezhang@xmu.edu.cn.
  • # Contributed equally.
PMID: 35732922 DOI: 10.1038/s41418-022-01027-7
Abstract

Alzheimer's disease (AD) is the most common form of neurodegenerative disease featured with memory loss and cognitive function impairments. Chronic mitochondrial stress is a vital pathogenic factor for AD and finally leads to massive neuronal death. However, the underlying mechanism is unclear. By proteomic analysis, we identified a new mitochondrial protein, cell-cycle exit and neuronal differentiation 1 (CEND1), which was decreased significantly in the brain of 5xFAD mice. CEND1 is a neuronal specific protein and locates in the presynaptic mitochondria. Depletion of CEND1 leads to increased mitochondrial fission mediated by upregulation of Dynamin related protein 1 (Drp1), resulting in abnormal mitochondrial functions. CEND1 deficiency leads to cognitive impairments in mice. Overexpression of CEND1 in the hippocampus of 5xFAD mice rescued cognitive deficits. Moreover, we identified that CDK5/p25 interacted with and phosphorylated CEND1 which promoted its degradation. Our study provides new mechanistic insights in mitochondrial function regulations by CEND1 in Alzheimer's disease.

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