A natural small molecule ‐mediated inhibition of alpha‐synuclein aggregation leads to neuroprotection in Caenorhabditis elegans

In this study, a small natural molecule shikonin has been explored for its anti-aggregation and neuroprotective activities. Shikonin significantly inhibited α-syn aggregation at equimolar and sub-stochiometric concentrations by stabilizing the monomers, increasing lag time and delaying elongation of α-syn fibrils. Also, inC. elegans PD models, shikonin showed neuroprotection and rescued neuronal degeneration by reducing α-syn aggregation, improving locomotor activity and preventing dopaminergic neuronal degeneration. The present study highlights the role of natural small molecules in the prevention of protein aggregation, that may further be explored for their therapeutic potential. AbstractSmall molecules are being explored intensively for their applications as therapeutic molecules in the management of metabolic and neurological disorders. The natural small molecules can inhibit protein aggregation and underlying cellular pathogenesis of neurodegenerative diseases involving multi-factorial mechanisms of action. Certain natural small molecular inhibitors of pathogenic protein aggregation are highly efficient and have shown promising therapeutic potential. In the present study, Shikonin (SHK), a natural plant-based naphthoquinone has been investigated for its aggregation inhibition activity against α-synuclein (α-syn) and the neuroprotective potential inCaenorhabditis elegans (C. elegans). SHK significantly inhibited aggregation of α-syn at sub-stochiometric concentrati...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research