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Epigenetics in Neurodegenerative Diseases.

Brigitte van Zundert1,2,3, Martin Montecino4,5

  • 1Faculty of Medicine and Faculty of Life Sciences, Institute of Biomedical Sciences (ICB), Universidad Andres Bello, Santiago, Chile. bvanzundert@unab.cl.

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|January 17, 2025
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Summary

Epigenetic changes in the brain impact gene expression, contributing to neurodegenerative diseases like Alzheimer's. Environmental factors and aging can drive these epigenetic modifications, offering new therapeutic targets.

Keywords:
3D chromatinBrainEnhancer-promoter interactionsEpidrugsEpigenetic editingEpigenomeNeurodegenerative diseases

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Area of Science:

  • Neuroscience
  • Genetics
  • Epigenetics

Background:

  • Neurodegenerative diseases (NDDs) like Alzheimer's (AD), ALS, and FTD involve genetic and non-genetic factors.
  • Healthy brain function relies on precise gene expression regulation via epigenetics and chromatin organization.

Purpose of the Study:

  • To explore how (epi)genomic and transcriptomic alterations in the brain relate to NDDs, particularly AD.
  • To review potential therapeutic strategies targeting epigenetic mechanisms.

Main Methods:

  • Analysis of global and locus-specific (epi)genomic and transcriptomic data from human and mouse brain samples.
  • Cell-type-specific resolution analysis to understand gene expression changes.

Main Results:

  • DNA methylation and histone marks dysregulate key genes in AD pathogenesis, neuroplasticity, and microglial activation.
  • Genetic risk variants in enhancers alter transcription by disrupting chromatin interactions.
  • Epigenomic erosion leads to transcriptional disruption and cell identity loss.
  • Environmental factors (aging, pollution, pesticides) induce epigenetic changes impacting AD pathways.

Conclusions:

  • Epigenetic dysregulation is a key mechanism in NDDs, influenced by genetics and environment.
  • Therapeutic strategies involving epigenetic editing and epidrugs show promise for treating NDDs.