2. Academic Validation
  3. Intergenerational epigenetic inheritance mediated by MYS-2/MOF in the pathogenesis of Alzheimer's disease

Intergenerational epigenetic inheritance mediated by MYS-2/MOF in the pathogenesis of Alzheimer's disease

  • iScience. 2024 Jul 25;27(8):110588. doi: 10.1016/j.isci.2024.110588.
Yuhong Li 1 2,  Hua Bai 1 3,  Wenwen Liu 1,  Wenhui Zhou 1,  Huan Gu 1,  Peiji Zhao 1,  Man Zhu 1 2,  Yixin Li 1,  Xinyi Yan 1,  Ninghui Zhao 4,  Xiaowei Huang 1
Affiliations

Affiliations

  • 1 School of Medicine, State Key Lab for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China.
  • 2 College of Biological Resources and Food Engineering, Qujing Normal University, Qujing 655000, China.
  • 3 School of Public Health, Kunming Medical University, Kunming 650500, China.
  • 4 Neurosurgery of the Second Hospital Affiliated with Kunming Medical University, Kunming 650101, China.
PMID: 39220410 DOI: 10.1016/j.isci.2024.110588
Abstract

Although autosomal-dominant inheritance is believed an important cause of familial clustering Alzheimer's disease (FAD), it covers only a small proportion of FAD incidence, and so we investigated epigenetic memory as an alternative mechanism to contribute for intergenerational AD pathogenesis. Our data in vivo showed that mys-2 of Caenorhabditis elegans that encodes a putative MYST acetyltransferase responsible for H4K16 acetylation modulated AD occurrence. The phenotypic improvements in the parent generation caused by mys-2 disfunction were passed to their progeny due to epigenetic memory, which resulted in similar H4K16ac levels among the candidate target genes of MYS-2 and similar gene expression patterns of the AD-related pathways. Furthermore, the ROS/CDK-5/ATM pathway functioned as an upstream activator of MYS-2. Our study indicated that MYS-2/MOF could be inherited intergenerationally via epigenetic mechanisms in C. elegans and mammalian cell of AD model, providing a new insight into our understanding of the etiology and inheritance of FAD.

Keywords

Cell biology; Epigenetics; Neuroscience.

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