Neurodegeneration, Heterochromatin, and Double-Stranded RNA

Abstract

Changes in chromatin and epigenetic modifications have been associated with aging and aging-associated neurodegenerative diseases, although the causal relationship between these changes and disease-related pathology has been unclear. Recent studies have now made direct connections between neurodegeneration-associated proteins and derepression of repetitive element transcription due to changes in heterochromatin. We suggest that this derepression leads to an increased accumulation of intracellular double-stranded RNA (dsRNA), with an attendant induction of innate immune responses that contribute to the neuroinflammation found in essentially all age-associated neurodegenerative diseases.