Front Mol Neurosci. 2022 Dec 8:15:1034766.doi: 10.3389/fnmol.2022.1034766. eCollection 2022.

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Nucleosome assembly protein 1-like 5 alleviates Alzheimer’s disease-like pathological characteristics in a cell model

Affiliations

Affiliations

  • 1 Department of Anesthesiology, The Second Hospital of Tianjin Medical University, Tianjin, China.
  • 2 Department of Pathogen Biology, School of Basic Medicine, Tianjin Medical University, Tianjin, China.
  • 3 Department of Physiology and Pathophysiology, School of Basic Medicine, Tianjin Medical University, Tianjin, China.

Abstract

Alzheimer’s disease (AD) remains one of the most common dementias of neurodegenerative disease-related diseases. Nucleosome assembly protein 1-like 5 (NAP1L5) belongs to the NAP1L protein family, which acts as a histone chaperone. However, the function and mechanism of NAP1L5 in AD are still unclear. Bioinformatics analysis, RT-qPCR, and Western blotting results showed that NAP1L5 was downregulated in the brain tissues of AD patients and a mouse cell model of AD. NAP1L5 overexpression alleviated (Amyloid-β precursor protein) APP metabolism and Tau phosphorylation. We further demonstrated that NAP1L5 regulated the AD-like pathological characteristics through the GSK3B/Wnt/β-Catenin signaling pathway. Moreover, we showed that the Wnt/β-Catenin signaling pathway, regulated by NAP1L5, was mediated by AQP1-mediated mechanism in N2a-APP695sw cell. In sum, these results suggested that NAP1L5 overexpression has neuroprotective effects and might act as potential biomarker and target for the diagnosis and treatment of AD.

Keywords: APP metabolism; Alzheimer’s disease; GSK3B; NAP1L5; Tau phosphorylation; Wnt/β-catenin signaling pathway; neuroinflammation.

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