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Neurodegeneration, Heterochromatin, and Double-Stranded RNA.

Tassa K Saldi1, Patrick K Gonzales2, Thomas J LaRocca2

  • 1Department of Biochemistry and Molecular Genetics, University of Colorado, Aurora, CO, USA.

Journal of Experimental Neuroscience
|February 23, 2019
PubMed
Summary
This summary is machine-generated.

Epigenetic changes in aging brains can cause repetitive DNA elements to activate, leading to double-stranded RNA (dsRNA) accumulation and neuroinflammation in neurodegenerative diseases.

Keywords:
Alzheimer diseaseFrontotemporal dementiaamyotrophic lateral sclerosis (ALS)repetitive elementsretro-transposonstauopathy

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Area of Science:

  • Neuroscience
  • Genetics
  • Immunology

Background:

  • Chromatin and epigenetic modifications are linked to aging and neurodegenerative diseases.
  • The causal link between these epigenetic changes and disease pathology remains unclear.

Purpose of the Study:

  • To explore the connection between neurodegeneration-associated proteins, heterochromatin changes, and repetitive element transcription.
  • To propose a mechanism linking epigenetic alterations to neuroinflammation in aging.

Main Methods:

  • Analysis of recent studies connecting neurodegeneration-associated proteins to heterochromatin.
  • Investigation of the consequences of derepressed repetitive element transcription.

Main Results:

  • Neurodegeneration-associated proteins are linked to the derepression of repetitive elements due to heterochromatin changes.
  • This derepression results in increased intracellular accumulation of double-stranded RNA (dsRNA).

Conclusions:

  • Accumulated dsRNA induces innate immune responses, contributing to neuroinflammation.
  • This mechanism provides a potential explanation for neuroinflammation in age-associated neurodegenerative diseases.