Unraveling comparative anti-amyloidogenic behavior of pyrazinamide and D-Cycloserine: A mechanistic biophysical insight

45Citations
Citations of this article
27Readers
Mendeley users who have this article in their library.

Abstract

Amyloid fibril formation by proteins leads to variety of degenerative disorders called amyloidosis. While these disorders are topic of extensive research, effective treatments are still unavailable. Thus in present study, two anti-tuberculosis drugs, i.e., pyrazinamide (PYZ) and D-cycloserine (DCS), also known for treatment for Alzheimer's dementia, were checked for the anti-aggregation and anti-amyloidogenic ability on Aβ-42 peptide and hen egg white lysozyme. Results demonstrated that both drugs inhibit the heat induced aggregation; however, PYZ was more potent and decelerated the nucleation phase as observed from various spectroscopic and microscopic techniques. Furthermore, pre-formed amyloid fibrils incubated with these drugs also increased the PC12/SH-SY5Y cell viability as compare to the amyloid fibrils alone; however, the increase was more pronounced for PYZ as confirmed by MTT assay. Additionally, molecular docking study suggested that the greater inhibitory potential of PYZ as compare to DCS may be due to strong binding affinity and more occupancy of hydrophobic patches of HEWL, which is known to form the core of the protein fibrils.

Cite

CITATION STYLE

APA

Chaturvedi, S. K., Zaidi, N., Alam, P., Khan, J. M., Qadeer, A., Siddique, I. A., … Khan, R. H. (2015). Unraveling comparative anti-amyloidogenic behavior of pyrazinamide and D-Cycloserine: A mechanistic biophysical insight. PLoS ONE, 10(8). https://doi.org/10.1371/journal.pone.0136528

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free