期刊
FREE RADICAL RESEARCH
卷 49, 期 2, 页码 139-150出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/10715762.2014.987274
关键词
Alzheimer's disease; apoptosis; A beta; neuroprotective effect; oxidative stress; beta-hydroxybutyrate
资金
- Natural Science Foundation of China [31101865]
Alzheimer's disease is a neurodegenerative disorder associated with the deposition of the peptide amyloid-beta (A beta) in senile plaques and cerebral vasculature. The neurotoxic mechanisms of this condition have been linked to oxidative-stress-induced apoptosis leading to widespread neuronal loss. Herein, we demonstrate the neuroprotective effects of a ketone body D-beta-hydroxybutyrate (beta-HB) in neural cell lines and an animal model induced by injecting A beta into the hippocampus. Using histological examination and the TUNEL assay, we show that administration of exogenous beta-HB effectively prevents A beta deposition and neuron apoptosis in this rat model. beta-HB pretreatment also relieves the oxidative stress in A beta-induced PC-12 cells, as shown by decreased intracellular reactive oxygen species and Ca2+ levels, activated Nrf2 and recovered superoxide dismutase and catalase activities. Consequently, the apoptotic pathway is also inhibited in these cells, with decreased levels of p53, caspase-12, caspase-9, caspase-3; a decreased Bax/Bcl-2 ratio; and decreased cytochrome c release. Taken together, our study provides a molecular basis for the neuroprotective effects of beta-HB in line with the suppression of oxidative stress and the inhibition of apoptotic protein activation.
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