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

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Relation http://ir.cftri.com/14678/
https://doi.org/10.1007/s11033-020-05393-8
 
Title Mechanism of rutin mediated inhibition of insulin amyloid formation
and protection of Neuro‑2a cells from fbril‑induced apoptosis.
 
Creator Mahendra, V. P.
Yogendra Prasad, K.
Ganesan, P.
Ravi, Kumar
 
Subject 13 Molecular Biochemistry
04 Diabetes Mellitus
 
Description Many metabolic and neurodegenerative diseases are associated with protein misfolding and aggregation. Insulin a key hormone, under certain conditions aggregates and forms pathological amyloid fbrils. Several polyphenols have been studied
extensively to elucidate their inhibitory efect on amyloid formation. In the present study, we used insulin as an amyloid model
to test the mechanism and efcacy 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 fbril formation. Further,
rutin interacts with insulin directly and inhibits fbril 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 fbril induced cytotoxicity and apoptosis. Rutin, decreases the insulin amyloid
fbrils-induced Neuro-2a cytotoxicity by reducing reactive oxygen species (ROS) levels which in turn downregulates Bax and
upregulates Bcl-2 and pBad proteins. These fndings suggest the potential action of rutin in preventing protein misfolding,
cell death, and serves as a lead structure to design novel anti-amyloidosis compounds.
 
Date 2020
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/14678/1/Molecular%20Biology%20Reports%20%282020%29%20472811%E2%80%932820.pdf
Mahendra, V. P. and Yogendra Prasad, K. and Ganesan, P. and Ravi, Kumar (2020) Mechanism of rutin mediated inhibition of insulin amyloid formation and protection of Neuro‑2a cells from fbril‑induced apoptosis. Molecular Biology Reports, 47. pp. 2811-2820. ISSN 0301-4851