Honokiol Alleviates Cognitive Deficits of Alzheimer's Disease (PS1V97L) Transgenic Mice by Activating Mitochondrial SIRT3

J Alzheimers Dis. 2018;64(1):291-302. doi: 10.3233/JAD-180126.


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.

Keywords: Alzheimer’s disease; amyloid-β protein; cognitive dysfunction; mitochondria; sirtuin 3 (SIRT3).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / chemistry
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Biphenyl Compounds / therapeutic use*
  • Cells, Cultured
  • Cognition Disorders / etiology*
  • Disease Models, Animal
  • Embryo, Mammalian
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Hippocampus / cytology
  • Lignans / therapeutic use*
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Neurons / drug effects
  • Neurons / ultrastructure
  • Oligoribonucleotides / pharmacology
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Presenilin-1 / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Sirtuin 3 / metabolism*


  • Amyloid beta-Peptides
  • Biphenyl Compounds
  • Enzyme Inhibitors
  • Lignans
  • Oligoribonucleotides
  • PSEN1 protein, human
  • Presenilin-1
  • Sirt3 protein, mouse
  • honokiol
  • Sirtuin 3