In a groundbreaking study, the Indian Institute of Technology Mandi has collaborated with international researchers to uncover critical insights into the treatment of Parkinson’s disease. The focus of the research was on Alpha-synuclein, a brain-abundant protein that undergoes increased phosphorylation in Parkinson’s patients.
Parkinson’s disease, a neurodegenerative disorder, has seen a rising prevalence globally, with a projected 200-300% increase in cases anticipated in India over the next two to three decades. Driven by the urgency of understanding the intricacies of this debilitating disease, an international team, including experts from IIT Mandi, medical schools, and pharmaceutical companies, delved into the nature of Alpha-synuclein.
Alpha-synuclein, a polymer chain of amino acids, exhibits heightened phosphorylation in patients with Parkinson’s disease, particularly at the 129th position. Phosphorylation, likened to a molecular master switch, involves the attachment of phosphate groups to proteins, influencing their activation or deactivation. Inhibiting phosphorylation at the 129th position has shown promise in potentially halting the progression of Parkinson’s.
Speaking about the significance of the study, Dr. Dube Dheeraj Prakashchand of IIT Mandi stated, “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 utilized a comprehensive array of techniques, including biochemical assays, protein analysis, and gene studies on mouse models. The team discovered that preventing the phosphorylation of Alpha-synuclein significantly impacted normal brain function, suggesting that α-syn Ser129P might act as a switch triggered by brain cell activity to initiate crucial signaling pathways.
In addition to experimental approaches, the researchers employed advanced computer modeling to gain insights into the structural changes caused by the phosphorylated protein. This modeling helped them understand how this modification enables Alpha-synuclein to interact with other proteins.
The findings of this research carry significant implications for the development of targeted therapies for Parkinson’s disease. Three practical applications include designing drugs or gene therapies to maintain correct levels of SER129 in specific brain areas, developing molecules to imitate or disrupt connections between proteins involving Ser129P, and enhancing disease models for studying the effects of Parkinson’s medications on Ser129P.
This groundbreaking study not only advances our understanding of Parkinson’s disease but also opens new avenues for the development of treatments that consider both healing the disease and preserving overall brain health. The collaborative effort highlights the importance of international research initiatives in tackling complex medical challenges.
