16/01/2026
NIMHANS researchers have uncovered a new mechanistic framework that advances our understanding of Lewy body formation—the pathological hallmark of synucleinopathies, including Parkinson’s disease.
The study was led by Dr. Padavattan Sivaraman and his team, with Ms. Sneha Jos as the lead author, from the Department of Biophysics at NIMHANS. The research was supported by Prof. B. Padmanabhan (Department of Biophysics, NIMHANS) and Prof. M. M. Srinivas Bharath (Department of Clinical Psychopharmacology and Toxicology, NIMHANS). This work was carried out in collaboration with Dr. Sangeeta Nath (MAHE, Bengaluru), Dr. Neelakandan’s team (inSTEM, Bengaluru), and Dr. Deepak Sharma (CSIR-IMTECH, Chandigarh), and has been published in the prestigious journal Communications Biology (Nature Portfolio).
DOI: https://rdcu.be/eYyjC
α-Synuclein (αSyn) is a key protein associated with synucleinopathies, including Parkinson’s disease. More than two decades ago, αSyn was identified as a major component of Lewy bodies (LBs). Since then, most studies have focused on linking αSyn aggregation and fibrillization with disease etiology. Both academia and industry have primarily focused on targeting aggregation using small molecules and antibodies as therapeutic strategies. Unfortunately, these approaches have not translated successfully in clinical trials.
For decades, the field has been guided by an αSyn-centric fibrillization model, which has overlooked the molecular complexity and heterogeneity of Lewy bodies. This narrow perspective has left a fundamental question unresolved:
How does α-synuclein sequester diverse biomolecules to drive Lewy body formation?
NIMHANS researchers have now addressed this critical gap and propose a new conceptual framework—the “Multifactorial Random Disorder Model.” This model extends beyond the traditional fibrillization-centric hypothesis, offering a broader understanding of how αSyn drives Lewy body formation in neurons.
The lead researcher, Dr. Sivaraman, believes that this work has the potential to reshape future strategies for biomarker and therapeutic development in Parkinson’s disease and related neurological disorders. Moreover, this new perspective strengthens the global effort to better understand and combat neurodegenerative disorders.
