Protein linked to Parkinson's also key for normal brain work: IIT Mandi study

MANDI: A protein involved in the progression of Parkinson’s disease also has a key role in regular brain function, revealed a study by the Indian Institute of Technology (IIT) Mandi on Thursday.

Parkinson’s disease is on the rise globally, with experts projecting a substantial 200-300 per cent increase in cases in India over the next two to three decades.

The international team of experts led by IIT Mandi used a comprehensive array of techniques to understand the nature of the protein, called Alpha-synuclein, in the progression of Parkinson’s disease.

Alpha-synuclein is abundantly found in the brain. In patients with Parkinson’s disease and related conditions, this protein is highly phosphorylated, that is, 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 a 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.

“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 alpha-synuclein protein, is not just a disease marker but also crucial for normal brain work,” said Dube Dheeraj Prakashchand, in a statement.

“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,” he added.

Through a combination of biochemical assays, protein analysis, and gene studies on mouse models, the researchers 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, they said.

The research findings may help design drugs or gene therapies to ensure that the levels of SER129 are maintained correctly in specific areas of the brain.

Molecules can also be designed to either imitate or disrupt the connections between proteins that involve Ser129P to treat diseases like Parkinson’s. Phosphorylated Ser129 models may also be used to check if Parkinson’s medications affect Ser129P in any way, the team said.