TY - JOUR
T1 - Protective effects of β-sheet breaker α/β-hybrid peptide against amyloid β-induced neuronal apoptosis in vitro
AU - Kumar, Sourav
AU - Paul, Ashim
AU - Kalita, Sourav
AU - Ghosh, Anup Kumar
AU - Mandal, Bhubaneswar
AU - Mondal, Amal Chandra
N1 - Publisher Copyright:
© 2016 John Wiley & Sons A/S.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Alzheimer's disease is most common neurodegenerative disorder and is characterized by increased production of soluble amyloid-β oligomers, the main toxic species predominantly formed from aggregation of monomeric amyloid-β (Aβ). Increased production of Aβ invokes a cascade of oxidative damages to neurons and eventually leads to neuronal death. This study was aimed to investigate the neuroprotective effects of a β-sheet breaker α/β-hybrid peptide (BSBHp) and the underlying mechanisms against Aβ40-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. Cells were pretreated with the peptide Aβ40 to induce neurotoxicity. Assays for cell viability, cell membrane damage, cellular apoptosis, generation of reactive oxygen species (ROS), intracellular free Ca2+, and key apoptotic protein levels were performed in vitro. Our results showed that pretreatment with BSBHp significantly attenuates Aβ40-induced toxicity by retaining cell viability, suppressing generation of ROS, Ca2+ levels, and effectively protects neuronal apoptosis by suppressing pro-apoptotic protein Bax and up-regulating antiapoptotic protein Bcl-2. These results suggest that α/β-hybrid peptide has neuroprotective effects against Aβ40-induced oxidative stress, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases.
AB - Alzheimer's disease is most common neurodegenerative disorder and is characterized by increased production of soluble amyloid-β oligomers, the main toxic species predominantly formed from aggregation of monomeric amyloid-β (Aβ). Increased production of Aβ invokes a cascade of oxidative damages to neurons and eventually leads to neuronal death. This study was aimed to investigate the neuroprotective effects of a β-sheet breaker α/β-hybrid peptide (BSBHp) and the underlying mechanisms against Aβ40-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. Cells were pretreated with the peptide Aβ40 to induce neurotoxicity. Assays for cell viability, cell membrane damage, cellular apoptosis, generation of reactive oxygen species (ROS), intracellular free Ca2+, and key apoptotic protein levels were performed in vitro. Our results showed that pretreatment with BSBHp significantly attenuates Aβ40-induced toxicity by retaining cell viability, suppressing generation of ROS, Ca2+ levels, and effectively protects neuronal apoptosis by suppressing pro-apoptotic protein Bax and up-regulating antiapoptotic protein Bcl-2. These results suggest that α/β-hybrid peptide has neuroprotective effects against Aβ40-induced oxidative stress, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases.
KW - Alzheimer's disease
KW - SH-SY5Y cell
KW - amyloid-β peptide
KW - apoptosis
KW - human cerebrospinal fluid
KW - neuroprotection
KW - β-sheet breaker α/β-hybrid peptide
UR - http://www.scopus.com/inward/record.url?scp=85007188776&partnerID=8YFLogxK
U2 - 10.1111/cbdd.12912
DO - 10.1111/cbdd.12912
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C2 - 27995757
AN - SCOPUS:85007188776
SN - 1747-0277
VL - 89
SP - 888
EP - 900
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
IS - 6
ER -
