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Unraveling Comparative Anti-Amyloidogenic Behavior of Pyrazinamide and
D-Cycloserine: A Mechanistic Biophysical Insight
#MMPMID26312749
Chaturvedi SK
; Zaidi N
; Alam P
; Khan JM
; Qadeer A
; Siddique IA
; Asmat S
; Zaidi Y
; Khan RH
PLoS One
2015[]; 10
(8
): e0136528
PMID26312749
show ga
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 A?-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.