New Delhi: A new study has described how molecular changes triggered by a viral infection may pave way for one to develop neurodegenerative diseases such as Parkinson’s disease.
Neurodegenerative diseases are marked by amyloid deposits in the brain – abnormal clumps formed when proteins aggregate together.
Researchers from the Council of Scientific and Industrial Research (CSIR)-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, said the amyloids hamper a transmission of information across neurons, leading to an impaired functioning.
In Parkinson’s disease, the protein ‘α-Synuclein’ forms amyloid clumps in the brains of patients.
“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,” Swasti Raychaudhuri, researcher at CSIR-CCMB and author of the study published in the journal Cell Reports, said.
“So, while not every viral infection leads to increased amyloid formation and neurodegenerative disease, (a) repeated exposure might tilt the odds against us,” Raychaudhuri said.
Several emerging studies have linked Influenza and COVID-19 to elevated risks of neurodegenerative diseases, including Parkinson’s disease, the researchers said.
Influenza and COVID-19, among other respiratory illnesses, are caused by RNA viruses — viruses that use RNA instead of DNA as their genetic material.
The study found that the viruses fold their RNA — genetic material folds continuously throughout the life of a cell — into special 3D structures, called ‘RNA G-quadruplexes’.
When viruses infect cells, the special 3D structures bind to α-Synuclein, accelerating the formation of amyloid clump, a hallmark of Parkinson’s disease, the researchers said.
Cells are equipped with a protective mechanism against viruses.
Upon infection, a helicase protein — an enzyme that unwinds DNA or RNA strands — called ‘DDX39A’ and usually housed in the cell’s nucleus, is released into the cytoplasm and binds to α-Synuclein and RNA G-quadruplexes, the team found.
The helicase protein unwinds the viral RNA G-quadruplexes, and offers a line of protection against viral infection, the researchers said.
“The virus fails to replicate with its RNA structures dismantled, and thus, the viral load in the cells decreases,” first author Aanchal, from CSIR-CCMB, said.
“At the same time, the unwinding of viral RNA’s secondary structure effectively slows down α-Synuclein amyloid formation,” Aanchal said.
Cells operate with a fine balance of molecules in them, and similar to every process in life, there exists a trade-off in the biomolecular interactions, the researchers said.
The authors “demonstrate that while DDX39A unwinds viral rG4s (RNA G-quadruplexes) to mitigate α-Synuclein sol-gel transition, its cooperative phase separation with α-Synuclein enhances the helicase’s rG4-unwinding activity.”
They “propose that (an) accelerated α-Synuclein amyloidogenesis reflects a trade-off within this RNA-protein equilibrium and might contribute to the viral etiology of PD (Parkinson’s disease).”
The team also included researchers from the Indian Institute of Technology Kharagpur.
