Affiliations: [a] Innovation Center for Neurological Disorders, Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China | [b] Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, P.R. China | [c] Clinical Center for Neurodegenerative Disease and MemoryImpairment, Capital Medical University, Beijing, P.R. China | [d] Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, P.R. China | [e] Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, P.R. China | [f] National Clinical Research Center forGeriatric Disorders, Beijing, P.R. China
Correspondence:
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Correspondence to: Jianping Jia, Innovation Center for Neurological Disorders, Xuan Wu Hospital, Capital Medical University, Beijing 100053, P.R. China. Tel.: +86 10 83199449; Fax: +86 10 83171070; E-mail: [email protected].
Abstract: Accumulating evidence has demonstrated that mitochondrial dysfunction is a prominent early event in the progression of Alzheimer’s disease (AD). Whether protecting mitochondrial function can reduce amyloid-β oligomer (AβO)-induced neurotoxicity in PS1V97L transgenic mice remains unknown. In this study, we examined the possible protective effects of honokiol (HKL) on mitochondrial dysfunction induced by AβOs in neurons, and cognitive function in AD PS1V97Ltransgenic mice. We determined that HKL increased mitochondrial sirtuin 3 (SIRT3) expression levels and activity, which in turn markedly improved ATP production and weakened mitochondrial reactive oxygen species production. We demonstrated that the enhanced energy metabolism and attenuated oxidative stress of HKL restores AβO-mediated mitochondrial dysfunction in vitro and in vivo. Consequently, memory deficits in the PS1V97L transgenic mice were rescued by HKL in the early stages. These results suggest that HKL has therapeutic potential for delaying the onset of AD symptoms by alleviating mitochondrial impairment and increasing hyperactivation of SIRT3 in the pathogenesis of preclinical AD.
