CCMB study links viral infections to Parkinson’s

Infections caused by certain viruses such as influenza and SARS-CoV-2, the virus responsible for COVID-19, are likely to cause neurodegenerative diseases like Parkinson’s disease, a new study by scientists at the Hyderabad-based CSIR-Centre for Cellular and Molecular Biology (CCMB) has found

Infections caused by certain viruses such as influenza and SARS-CoV-2, the virus responsible for COVID-19, are likely to cause neurodegenerative diseases like Parkinson’s disease, a new study by scientists at the Hyderabad-based CSIR-Centre for Cellular and Molecular Biology (CCMB) has found.

India News

An official release from the CCMB said the study, led by Dr Swasti Raychaudhuri’s laboratory and published in the peer-reviewed journal “Cell Reports,” provides new insights into how viral infections could promote the formation of abnormal protein clumps associated with neurodegenerative diseases.

The CCMB study focuses on alpha-synuclein, a protein that plays a central role in Parkinson’s disease. Under certain conditions, this protein can clump together to form amyloid deposits in the brain. These abnormal deposits can interfere with communication between nerve cells and impair their functioning.

The researchers found that RNA viruses may influence this process through unusual structures formed by their genetic material. “Unlike DNA, RNA is a single-stranded molecule, but it can fold into complex shapes. One such structure is known as an RNA G-quadruplex (rG4). According to the study, these structures formed by viral RNA can interact with alpha-synuclein and accelerate the formation of amyloid clumps,” the study said.

The researchers also identified a natural cellular defence mechanism that can counter this process. “When a cell is infected by an RNA virus, a protein called DDX39A, which normally remains inside the cell nucleus, moves into the surrounding cell fluid, or cytoplasm. There, it binds to both alpha-synuclein and the virus’s RNA structures,” it said.

DDX39A acts like a molecular “unwinding” machine. It breaks apart the rG4 structures in viral RNA, making it more difficult for the virus to reproduce. This, in turn, can reduce the amount of virus present inside infected cells.

The same process also appears to reduce the formation of alpha-synuclein amyloids. “The virus fails to replicate with its RNA structures dismantled, and thus, the viral load in the cells decreases. At the same time, the unwinding of viral RNA’s secondary structure effectively slows down alpha-synuclein amyloid formation,” said Aanchal, the first author of the study.

Dr Raychaudhuri said cells have several protective mechanisms that work to maintain a balance between competing molecular processes. Depending on the circumstances, these mechanisms may not always be sufficient to prevent amyloid formation.

“Even if there are protective mechanisms in the cells to prevent viral infections and avoid amyloid formation, there are situations that favour one kind of reaction more than the other. These decide the final outcomes in cells, and sometimes amyloid formation is accelerated in virus-infected cells,” he said.

He added that not every viral infection leads to increased amyloid formation and neurodegenerative disease, but repeated exposure might tilt the odds against us,

The researchers at CCMB are now studying the finer details of how an apparently routine viral infection could potentially initiate molecular changes that remain unnoticed for years and may contribute to Parkinson’s disease much later in life.