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Deciphering the enhanced inhibitory, disaggregating and cytoprotective potential of promethazine towards amyloid fibrillation.

Authors :
Nusrat S
Zaman M
Masroor A
Siddqi MK
Zaidi N
Neelofar K
Abdelhameed AS
Khan RH
Source :
International journal of biological macromolecules [Int J Biol Macromol] 2018 Jan; Vol. 106, pp. 851-863. Date of Electronic Publication: 2017 Aug 16.
Publication Year :
2018

Abstract

Increasing evidence proposed that amyloid deposition by proteins play a crucial role in an array of neurotoxic and degenerative disorders like Parkinson's disease, systemic amyloidosis etc, that could be controlled by anti-aggregation methodologies which either inhibit or disaggregate such toxic aggregates. The present work targets the amyloid inhibiting and disaggregating potential of promethazine (PRM) against human insulin (HI) and human lysozyme (HL) fibrillogenesis. Biophysical techniques like Rayleigh scattering measurements (RLS), Thioflavin T (ThT) and 8-Anilinonaphthalene-1-sulfonic acid (ANS) fluorescence measurement, circular dichroism (CD) and dynamic light scattering (DLS) measurements illustrated the inhibitory action of PRM. The half maximal inhibitory concentration (IC <subscript>50</subscript> ) of PRM for HI and HL was estimated to be 114.81±1.21μM and 186.20±1.03μM, respectively. Microscopic techniques revealed the absence of fibrillar structures when HI and HL was co-incubated with PRM. Cytoprotective behavior of PRM was investigated by cell based cytotoxicity assay performed on SH-SY5Y neuronal cell lines. The half maximal disaggregation concentration (DC <subscript>50</subscript> ) was calculated as 21.37±0.89μM and 45.70±0.76μM, signifying that PRM is much potent to disaggregate pre formed fibrils rather than to inhibit fibrillation. Thus, PRM could be beneficial as therapeutic agent that can aid in the cure of amyloid related diseases.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1879-0003
Volume :
106
Database :
MEDLINE
Journal :
International journal of biological macromolecules
Publication Type :
Academic Journal
Accession number :
28823512
Full Text :
https://doi.org/10.1016/j.ijbiomac.2017.08.081