Protective effects of ß-sheet breaker α/ß-hybrid peptide against amyloid ß-induced neuronal apoptosis in vitro.

ABSTRACT

Alzheimer's disease is most common neurodegenerative disorder and is characterized by increased production of soluble amyloid-ß oligomers, the main toxic species predominantly formed from aggregation of monomeric amyloid-ß (Aß). Increased production of Aß 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 ß-sheet breaker α/ß-hybrid peptide (BSBHp) and the underlying mechanisms against Aß40 -induced neurotoxicity in human neuroblastoma SH-SY5Y cells. Cells were pretreated with the peptide Aß40 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 Aß40 -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/ß-hybrid peptide has neuroprotective effects against Aß40 -induced oxidative stress, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases.