Free Radic. Biol. Med.

Alzheimer disease (AD) is characterized by extracellular senile plaques, intracellular neurofibrillary tangles, and memory loss. Aggregated amyloid-P (A beta), oxidative stress, and inflammation have pivotal roles in the pathogenesis of AD. Therefore, the inhibition of A beta-induced neurotoxicity, oxidative stress, and inflammation is a potential therapeutic strategy for the treatment of AD. In this study, a heptapeptide, isolated from a Ph.D.-C7C library by phage display, attenuated A beta 42-induced cytotoxicity in SH-SY5Y neuroblastoma cells and reduced A beta 42-induced oxidative stress by decreasing the production of reactive oxygen species and glutathione disulfide. As a result, glutathione level increased and superoxide dismutase and glutathione peroxidase activities were enhanced in vitro and in vivo. This peptide also suppressed the inflammatory response by decreasing the release of proinflammatory cytokines, such as tumor necrosis factor alpha and interleukin 1 beta, in microglia and by reducing microgliosis and astrogliosis in AD transgenic mice. This peptide was intracerebroventricularly administered to APPswe/PS1dE9 transgenic mice. We found that this peptide significantly improved spatial memory and reduced the amyloid plaque burden and soluble and insoluble A beta levels. Our findings suggest that this multifunctional peptide has therapeutic potential for an A beta-targeted treatment of AD. (C) 2014 Elsevier Inc. All rights reserved.Alzheimer disease (AD) is characterized by extracellular senile plaques, intracellular neurofibrillary tangles, and memory loss. Aggregated amyloid-P (A beta), oxidative stress, and inflammation have pivotal roles in the pathogenesis of AD. Therefore, the inhibition of A beta-induced neurotoxicity, oxidative stress, and inflammation is a potential therapeutic strategy for the treatment of AD. In this study, a heptapeptide, isolated from a Ph.D.-C7C library by phage display, attenuated A beta 42-induced cytotoxicity in SH-SY5Y neuroblastoma cells and reduced A beta 42-induced oxidative stress by decreasing the production of reactive oxygen species and glutathione disulfide. As a result, glutathione level increased and superoxide dismutase and glutathione peroxidase activities were enhanced in vitro and in vivo. This peptide also suppressed the inflammatory response by decreasing the release of proinflammatory cytokines, such as tumor necrosis factor alpha and interleukin 1 beta, in microglia and by reducing microgliosis and astrogliosis in AD transgenic mice. This peptide was intracerebroventricularly administered to APPswe/PS1dE9 transgenic mice. We found that this peptide significantly improved spatial memory and reduced the amyloid plaque burden and soluble and insoluble A beta levels. Our findings suggest that this multifunctional peptide has therapeutic potential for an A beta-targeted treatment of AD. (C) 2014 Elsevier Inc. All rights reserved