Fig. 6: A mechanism of circRNA reduction in Parkinson’s disease.
From: Early-stage idiopathic Parkinson’s disease is associated with reduced circular RNA expression
Innate immune responses can be induced by double-stranded RNA (dsRNA). A-I RNA editing by ADAR suppresses immune detection of endogenous dsRNA149 and influences circRNA synthesis53,54,77,78. Under normal conditions, circRNAs bound to PKR (encoded by EIF2AK2) act as inhibitors, undergoing degradation when activation is required50. Activation of the endonuclease RNase L as part of an antiviral immune response leads to degradation of circRNAs50. Decreased circRNAs in idiopathic PD could result in increased PKR, available for activation. Once activated, PKR phosphorylates eIF2α, initiating the integrated stress response (ISR)81.
