TY - JOUR
T1 - Bacoside-A, an Indian Traditional-Medicine Substance, Inhibits β-Amyloid Cytotoxicity, Fibrillation, and Membrane Interactions
AU - Malishev, Ravit
AU - Shaham-Niv, Shira
AU - Nandi, Sukhendu
AU - Kolusheva, Sofiya
AU - Gazit, Ehud
AU - Jelinek, Raz
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/4/19
Y1 - 2017/4/19
N2 - Bacoside-A, a family of compounds extracted from the Bacopa monniera plant, is a folk-medicinal substance believed to exhibit therapeutic properties, particularly enhancing cognitive functions and improving memory. We show that bacoside-A exerted significant inhibitory effects upon cytotoxicity, fibrillation, and particularly membrane interactions of amyloid-beta (1-42) (Aβ42), the peptide playing a prominent role in Alzeheimer's disease progression and toxicity. Specifically, preincubation of bacoside-A with Aβ42 significantly reduced cell toxicity and inhibited fibril formation both in buffer solution and, more significantly, in the presence of membrane vesicles. In parallel, spectroscopic and microscopic analyses reveal that bacoside-A blocked membrane interactions of Aβ42, while formation of Aβ42 oligomers was not disrupted. These interesting phenomena suggest that inhibition of Aβ42 oligomer assembly into mature fibrils, and blocking membrane interactions of the oligomers are likely the underlying factors for ameliorating amyloid toxicity by bacoside-A and its putative physiological benefits.
AB - Bacoside-A, a family of compounds extracted from the Bacopa monniera plant, is a folk-medicinal substance believed to exhibit therapeutic properties, particularly enhancing cognitive functions and improving memory. We show that bacoside-A exerted significant inhibitory effects upon cytotoxicity, fibrillation, and particularly membrane interactions of amyloid-beta (1-42) (Aβ42), the peptide playing a prominent role in Alzeheimer's disease progression and toxicity. Specifically, preincubation of bacoside-A with Aβ42 significantly reduced cell toxicity and inhibited fibril formation both in buffer solution and, more significantly, in the presence of membrane vesicles. In parallel, spectroscopic and microscopic analyses reveal that bacoside-A blocked membrane interactions of Aβ42, while formation of Aβ42 oligomers was not disrupted. These interesting phenomena suggest that inhibition of Aβ42 oligomer assembly into mature fibrils, and blocking membrane interactions of the oligomers are likely the underlying factors for ameliorating amyloid toxicity by bacoside-A and its putative physiological benefits.
KW - amyloid-membrane interactions
KW - bacoside-A
KW - fibrillation inhibitors
KW - fluorescence anisotropy
KW - giant vesicles
KW - β-Amyloid
KW - β-amyloid oligomers
UR - http://www.scopus.com/inward/record.url?scp=85018521886&partnerID=8YFLogxK
U2 - 10.1021/acschemneuro.6b00438
DO - 10.1021/acschemneuro.6b00438
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AN - SCOPUS:85018521886
SN - 1948-7193
VL - 8
SP - 884
EP - 891
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 4
ER -