This Project Grant award of $414,191 from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) supports research to investigate the relationship between the structural conformation of alpha-synuclein (α-syn) fibrils and the emergence of distinct pathological features in synucleinopathies like Lewy body dementia, Parkinson's disease, and multiple system atrophy. The research aims to employ a multidisciplinary approach combining biophysical analysis, molecular biology, and organ-on-a-chip technology to characterize the functional properties of polymorphic α-syn fibrils and examine their interactions with diverse cellular environments in a vascularized human midbrain tissue model. The expected outcomes will provide new insights into the molecular mechanisms underlying conformation-dependent neuropathology, which can inform the development of diagnostic and therapeutic strategies for synucleinopathies.
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