title: Unraveling Comparative Anti-Amyloidogenic Behavior of Pyrazinamide and D-Cycloserine: A Mechanistic Biophysical Insight.
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.
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.
authors: Sumit Kumar
authors: SK
authors: Chaturvedi
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.
authors: Nida
authors: N
authors: Zaidi
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.
authors: Parvez
authors: P
authors: Alam
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.
authors: Javed Masood
authors: JM
authors: Khan
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.
authors: Atiyatul
authors: A
authors: Qadeer
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.
authors: Ibrar Ahmad
authors: IA
authors: Siddique
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.
authors: Shamoon
authors: S
authors: Asmat
authors: Department of Zoology, Aligarh Muslim University, Aligarh, 202002, India.
authors: Yusra
authors: Y
authors: Zaidi
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.
authors: Rizwan Hasan
authors: RH
authors: Khan
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000737:chemistry* / Q000494:pharmacology; D002645:Chickens; D003523:Cycloserine / Q000737:chemistry* / Q000494:pharmacology; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D066329:Protein Aggregates; D011718:Pyrazinamide / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D000904:Antibiotics, Antitubercular; D010446:Peptide Fragments; D066329:Protein Aggregates; C075222:amyloid beta-protein (1-42); D011718:Pyrazinamide; D003523:Cycloserine; D009113:Muramidase