CCMB study links viral RNA structures to Parkinson's protein clumping
A CCMB study finds that RNA viruses like influenza and SARS-CoV-2 can promote alpha-synuclein aggregation, but a cellular protein DDX39A can counter it.
Infections caused by RNA viruses such as influenza and SARS-CoV-2 may set off molecular processes associated with Parkinson's disease, according to a new study by scientists at the CSIR-Centre for Cellular and Molecular Biology (CCMB). The work also points to a natural cellular defence mechanism that can limit the damage.
The team, led by Swasti Raychaudhuri, examined how these viruses trigger changes tied to neurodegeneration, a class of disorders marked by the buildup of abnormal protein deposits in the brain. Such clumps disrupt communication between neurons and impair their function over time.
The researchers focused on alpha-synuclein, a protein that forms toxic aggregates in the brains of people with Parkinson's disease. Unlike humans, whose genetic material is stored as DNA, these viruses carry their genetic information in RNA. This viral RNA can fold into specialised three-dimensional shapes known as RNA G-quadruplexes (rG4s).
The study found that during infection, these rG4 structures can bind to alpha-synuclein and promote its aggregation, a process linked to Parkinson's disease.
However, the team also identified a protective response. A protein called DDX39A, normally found in the cell nucleus, moves into the cytoplasm during infection and interacts with both alpha-synuclein and the viral rG4 structures. DDX39A can unwind these viral RNA structures, reducing the virus's ability to replicate and slowing the formation of harmful alpha-synuclein aggregates.
"The virus fails to replicate when its RNA structures are dismantled. This lowers the viral load and effectively slows alpha-synuclein amyloid formation," said Aanchal, the study's first author.
Raychaudhuri said the balance between harmful and protective cellular responses ultimately determines the outcome. While cells have mechanisms to fight viral infections and prevent the buildup of abnormal proteins, certain conditions may favour protein aggregation.
The researchers stressed that not every viral infection will lead to neurodegeneration. However, repeated viral infections could increase the likelihood of harmful changes accumulating over time. The team is now investigating how seemingly routine viral infections could contribute to the development of Parkinson's disease years later.