The Newz Radar
MANDI: A researcher from the Indian Institute of Technology at Mandi, in collaboration with international collaborators, has investigated a crucial protein involved in the progression of Parkinson’s disease.
The work by Dube Dheeraj Prakashchand, Assistant Professor, School of Mechanical & Materials Engineering, IIT-Mandi, after teaming up with Padmini Rangamani and lead author Subhojit Roy (both from University of California, San Diego, US), has offered the key insight that a protein modification seen in Parkinson’s also has a normal role in regular brain function. Other researchers are from Baylor College of Medicine, US, and Emory University, Atlanta, US.
Parkinson’s disease is on the rise globally, with experts projecting a substantial 200-300% increase in cases in India over the next two to three decades. Researchers worldwide are actively engaged in unravelling the complexities of this disease, from its causes and progression to understanding patterns and outcomes.
The international team of experts from various universities, including IIT-Mandi, medical schools and pharmaceutical companies, has used a comprehensive array of techniques to understand the nature of one particular protein that has been associated with Parkinson’s disease. The protein, called Alpha-synuclein, is abundantly found in the brain. In patients with Parkinson’s disease and related conditions, this protein is highly phosphorylated i.e., phosphate groups attached to one amino acid (serine-129) of this protein.
Considering Phosphorylation akin to a master switch at the molecular level, which involves a minute phosphate (-PO4 group latching onto proteins. This action is similar to flipping a switch, ingeniously activating or deactivating these proteins thereby finetuning its ambience for molecular interactions which lead to the progression of Parkinson’s. Alpha-synuclein, like other proteins, being polymer chain of amino acids, has a prominent phosphorylation site at the 129th position in the chain which when inhibited results in potentially halting the progression of Parkinson’s.
Speaking about the research, Prakashchand said, “This important study changes how we think about a protein change linked to Parkinson’s disease. It shows that this change, called phosphorylation at a certain site on the α-synuclein protein, is not just a disease marker but also crucial for normal brain work. The research suggests that stopping this process might harm brain function, leading to new ways to think about treating Parkinson’s that consider both healing the disease and keeping the brain healthy.”
Through a combination of biochemical assays, protein analysis and gene studies on mouse models, the international research team examined the protein and its phosphorylation patterns. When the phosphorylation of this protein was prevented, it significantly impacted normal brain function, suggesting that a-syn Ser129P might act as a switch triggered by brain cell activity to initiate crucial signalling pathways.
The researchers also used advanced computer modelling to gain insights into the structural changes caused by the phosphorylated protein, helping to understand how this modification enables the protein to interact with other proteins.
