Mechanism of rutin mediated inhibition of insulin amyloid formation and protection of Neuro-2a cells from fibril-induced apoptosis.

Mechanism of rutin mediated inhibition of insulin amyloid formation and protection of Neuro-2a cells from fibril-induced apoptosis. Mol Biol Rep. 2020 Apr 02;: Authors: Mahendra VP, Yogendra Prasad K, Ganesan P, Kumar R Abstract Many metabolic and neurodegenerative diseases are associated with protein misfolding and aggregation. Insulin a key hormone, under certain conditions aggregates and forms pathological amyloid fibrils. Several polyphenols have been studied extensively to elucidate their inhibitory effect on amyloid formation. In the present study, we used insulin as an amyloid model to test the mechanism and efficacy of rutin as an anti-amyloidogenic molecule. By using electron microscopy, dynamic light scattering and circular dichroism spectroscopy, we show that rutin inhibits the insulin aggregate and fibril formation. Further, rutin interacts with insulin directly and inhibits fibril formation in a dose-dependent manner as demonstrated by micro scale thermophoresis experiments. The molecular docking study predicted the potential binding pocket of rutin at the interface of chain A and chain B of insulin thereby preventing it from forming the aggregates. Since, rutin is a natural anti-oxidant, we studied its role in diminishing amyloid fibril induced cytotoxicity and apoptosis. Rutin, decreases the insulin amyloid fibrils-induced Neuro-2a cytotoxicity by reducing reactive oxygen species (ROS) levels which in turn downregulate...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research