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

Nusrat, S. and Zaman, M. and Masroor, A. and Siddqi, M.K and Zaidi, N. and Neelofar, K. and Abdelhameed, A.S. and Khan, R.H. (2018) Deciphering the enhanced inhibitory, disaggregating and cytoprotective potential of promethazine towards amyloid fibrillation. International Journal of Biological Macromolecules, 106. pp. 851-863. ISSN 1418130

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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 (IC50) of PRM for HI and HL was estimated to be 114.81 ± 1.21 μM and 186.20 ± 1.03 μM, 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 (DC50) was calculated as 21.37 ± 0.89 μM and 45.70 ± 0.76 μM, 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. © 2017 Elsevier B.V.

Item Type: Article
Uncontrolled Keywords: Amyloids; Disaggregation; Human insulin; Human lysozyme; IC50; Molecular docking
Subjects: R Medicine > R Medicine (General)
Divisions: Centres > Interdisciplinary Biotechnology Unit
Depositing User: AMU Library
Date Deposited: 18 Jan 2018 09:30
Last Modified: 11 Feb 2018 13:04
URI: http://ir.amu.ac.in/id/eprint/10783

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