Unlocking the epigenetic symphony: histone acetylation's impact on neurobehavioral change in neurodegenerative disorders

Epigenomics. 2024 Mar;16(5):331-358. doi: 10.2217/epi-2023-0428. Epub 2024 Feb 7.

Abstract

Recent genomics and epigenetic advances have empowered the exploration of DNA/RNA methylation and histone modifications crucial for gene expression in response to stress, aging and disease. Interest in understanding neuronal plasticity's epigenetic mechanisms, influencing brain rewiring amid development, aging and neurodegenerative disorders, continues to grow. Histone acetylation dysregulation, a commonality in diverse brain disorders, has become a therapeutic focus. Histone acetyltransferases and histone deacetylases have emerged as promising targets for neurodegenerative disorder treatment. This review delves into histone acetylation regulation, potential therapies and future perspectives for disorders like Alzheimer's, Parkinson's and Huntington's. Exploring genetic-environmental interplay through models and studies reveals molecular changes, behavioral insights and early intervention possibilities targeting the epigenome in at-risk individuals.

Keywords: Alzheimer's disease; Huntington's disease; Parkinson's disease; chromatin; neuronal loss; post-translational modifications.

Plain language summary

Scientists have made progress in understanding how our genes and their chemical modifications play a role in how our brains respond to stress, age and diseases. They are particularly interested in how these processes affect the flexibility of our brain circuits, which is important during growth and aging and in conditions like Alzheimer's and Parkinson's. One key area of focus is controlling a specific chemical change called histone acetylation, which tends to go awry in various brain disorders. Researchers are looking at potential treatments that target specific proteins related to this process. This review explores how these chemical changes might be regulated, potential treatments and the future for disorders like Alzheimer's, Parkinson's and Huntington's. By studying the interaction between our genes and the environment, scientists are uncovering changes at the molecular level, gaining insights into behavior and exploring ways to intervene early for people who are at risk.

Publication types

  • Review

MeSH terms

  • Acetylation
  • DNA Methylation
  • Epigenesis, Genetic
  • Histones* / metabolism
  • Humans
  • Neurodegenerative Diseases* / genetics

Substances

  • Histones