Circular RNAs emerge as mechanistic link between neurotropic viral infections and neurodegenerative diseases

The brain's aging process and the onset of neurodegenerative diseases like Alzheimer's disease and Parkinson's disease are complex, often involving neuroinflammation, synaptic dysfunction, and neuronal apoptosis. Current treatments primarily manage symptoms, failing to address underlying mechanisms or prevent progression. Growing evidence implicates neurotropic viral infections in contributing to long-term neurological sequelae, yet a direct mechanistic bridge between viral neuropathogenesis and neurodegeneration has remained elusive. Circular RNAs (circRNAs), highly stable RNA molecules, are emerging as critical regulators in both these distinct pathological processes, suggesting a potential, previously unintegrated, intersection.

This comprehensive review systematically evaluated the most updated research evidence on the roles of circular RNAs (circRNAs) in major neurodegenerative diseases and neurotropic viral infections. The authors synthesized findings from various studies to identify specific circRNAs linked to disease progression, their regulatory functions, and their involvement in both host antiviral responses and viral replication strategies. The review aimed to integrate these findings into a unified mechanistic framework, highlighting the potential for circRNAs to serve as biomarkers and therapeutic targets for age-related and virus-associated neurological disorders.

The review identified specific circRNAs linked to the progression of Alzheimer's disease and Parkinson's disease, where they regulate central pathological processes including amyloid-β clearance, neuroinflammation, synaptic plasticity, neuronal apoptosis, and oxidative stress. Both host cells and viruses produce circRNAs during infection. Virus-derived circRNAs can enhance viral replication, promote immune evasion, and support latency. Conversely, host circRNAs contribute to antiviral defense by acting as microRNA sponges, interacting with viral proteins, or encoding peptides with antiviral activity. The authors propose that dysregulated circRNAs may represent a crucial mechanistic link between viral infection and associated neurodegenerative processes, especially considering the growing concern regarding chronic neuroinflammation, viral reactivation, and post-viral syndromes. This integration suggests a novel perspective on disease etiology.

No studies have yet directly integrated circRNAs, neurotropic viral infections, and neurodegenerative disorders within a single mechanistic framework, underscoring the review's unique contribution.