CCMB study identifies possible link between RNA viruses and Parkinson’s processes

A study by scientists at the CSIR-Centre for Cellular and Molecular Biology has identified a possible mechanism through which infections with RNA viruses may trigger molecular processes associated with Parkinson’s disease. The researchers examined infections caused by viruses including influenza and SARS-CoV-2. Their work focused on alpha-synuclein, a protein that can form toxic aggregates in the brains of people with Parkinson’s disease.

The team found that viral RNA can fold into specialised three-dimensional structures known as RNA G-quadruplexes, or rG4s. When viruses infect cells, these structures can bind to alpha-synuclein and promote its aggregation, a process linked to neurodegeneration. The study also identified a natural cellular defence mechanism.

The protein DDX39A, normally located in the cell nucleus, moves into the cytoplasm during infection and interacts with both alpha-synuclein and viral rG4 structures. According to the researchers, DDX39A can unwind the viral RNA structures. This reduces the virus’s ability to replicate and slows the formation of harmful alpha-synuclein aggregates.

Aanchal, the study’s first author, said dismantling the structures lowers the viral load and slows amyloid formation. Swasti Raychaudhuri, who led the team, said the outcome depends on the balance between harmful and protective responses inside infected cells. The researchers stressed that not every viral infection will lead to neurodegeneration.

The team said repeated infections could increase the likelihood of harmful changes accumulating over time. It is now investigating how apparently routine viral infections might contribute to Parkinson’s-related changes years later. The findings were reported in a press release.