Scientists at NIMHANS, Bengaluru have found new clues about how Parkinson’s Disease (PD) begins at the molecular level. Their study shows that disease-specific chemical changes in α-Synuclein, a key protein linked to Parkinson’s, can trap other proteins early on. This may lead to the formation of Lewy bodies, the harmful protein clumps found in brain cells, before visible protein build-up appears. Parkinson’s is known for loss of dopamine neurons and α-Synuclein buildup. For years, drug research focused on stopping α-Synuclein fibrils, or clumps, but many drugs failed. Dr. Padavattan Sivaraman from NIMHANS explained, "Our findings suggest that early, disease-specific mis-interactions of αSyn monomers may be key events that initiate Lewy body assembly." The team studied two common Parkinson’s-linked changes in αSyn — C-terminal truncation and serine-129 phosphorylation. These changes alter the protein’s charge and shape, making it sticky and cause it to bind wrongly with many proteins, unlike the normal protein which binds more specifically. These sticky, modified αSyn proteins act like molecular adhesives, gathering diverse proteins and parts of cells into dense clusters. This could explain how Lewy bodies form and grow. Previous research supports this, showing modified αSyn at Lewy body cores and edges. Dr. Sivaraman said, "Instead of focusing only on fibrillization properties, therapies should also aim to prevent abnormal binding behaviour of disease-modified αSyn variants." This discovery is important for India, where Parkinson’s cases are rising. The average age of diagnosis is 51, younger than the global average of 60. Early detection and new drug targets could reduce the growing burden. The research, published in Communications Biology on January 8, was done with collaborators from other Indian institutes. It adds to NIMHANS’ fight against Parkinson’s, combining biophysics and brain studies to solve how this disease starts inside cells.