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Deterioration of mental functions during aging and Alzheimers disease (AD) progression is always accompanied by loss of neurons, presumably through apoptosis.The aim of the study is to investigate the effects of SS31 peptide on cognitive impairment and neuronal degeneration in the hippocampus of SAMP8 mice, as well as the potential mechanism.The cognitive function was tested by Morris Water Maze, neuronal changes in morphology in the CA1 and CA3 subregions of hippocampus were tested by Nissls staining with cresyl violet.Intraperitoneal injection of SS31 peptide with a dose of 2 mg/kg daily and 5 mg/kg daily for 8 weeks apparently alleviated cognitive disorders and neuronal damage.Western blot analyses demonstrated that SS31 peptide significantly decreased Bax/Bcl2 ratio in the hippocampus of SAMP8 mice.In addition, SS31 peptide effectively attenuated the upregulation of the mitochondrial matrix protein cyclophilin D (CypD) expression.Our findings suggest that SS31 peptide may be a potential neuroprotective agent through against apoptosis.