The study focused on Alpha-synuclein, a brain-abundant protein that shows increased phosphorylation in Parkinson’s patients.
Researcher from the Indian Institute of Technology Mandi in collaboration with international collaborators have investigated a crucial protein involved in the progression of Parkinson’s disease. Work by Dr. Dube Dheeraj Prakashchand, Assistant Professor, School of Mechanical & Materials Engineering, IIT Mandi – teaming up with Ms. Padmini Rangamani, PhD, and lead author Dr. Subhojit Roy, MD, PhD (both from University of California, San Diego, USA) – 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, USA, and Emory University, Atlanta, USA.
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, Dr. Dube Dheeraj 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 ?-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 signaling pathways.
The researchers also used advanced computer modeling 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.
The research findings have three practical implications.
? First, drugs or gene therapies can be designed to ensure that the levels of SER129 are maintained correctly in specific areas of the brain.
? Secondly, molecules can be designed to either imitate or disrupt the connections between proteins that involve Ser129P to treat diseases like Parkinson’s.
? Lastly, using this understanding of phosphorylated Ser129, models to study diseases like Parkinson’s, can be improved. These models can be used to check if Parkinson’s medications affect Ser129P in any way.
A senior journalist who has spent more than a decade in the profession, working for Amar Ujala and Aapka Faisla.
