Involvement of intracellular and mitochondrial Aβ in the ameliorative effects of huperzine A against oligomeric Aβ42-induced injury in primary rat neurons

Yun Lei, Ling Yang, Chun Yan Ye, Ming Yan Qin, Huai Yu Yang, Hua Liang Jiang, Xi Can Tang, Hai Yan Zhang

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Considerable studies indicate huperzine A is a promising natural product to suppress neuronal damages induced by β-amyloid (Aβ), a key pathogenic event in the Alzheimer's disease (AD). As an extension, the present study for the first time explored whether the beneficial profiles of huperzine A against oligomeric Aβ42 induced neurotoxicity are associated with the accumulation and detrimental function of intraneuronal/mitochondrial Aβ, on the basis of the emerging evidence that intracellular Aβ is more relevant to AD progression as compared with extracellular Aβ. Huperzine A treatment was shown to significantly attenuate the neurotoxicity of oligomeric Aβ42, as demonstrated by increased neuronal viability. Interestingly, our results proved that exogenous Aβ42 could accumulate intraneuronally in a dose- and time-dependent manner, while huperzine A treatment markedly reduced the level of intracellular Aβ42. Moreover, huperzine A treatment rescued mitochondrial dysfunction induced by oligomeric Aβ42, including adenosine triphosphate (ATP) reduction, reactive oxygen species (ROS) overproduction and membrane potential depolarization. Further study demonstrated that huperzine A also significantly reduced the level of Aβ42 in the mitochondria-enriched subcellular fractions, as well as the Aβ42 fluorescent signals colocalized with mitochondrial marker. This study indicates that interfering intracellular Aβ especially mitochondrial Aβ accumulation, together with ameliorating Aβ-associated mitochondrial dysfunction, may contribute to the protective effects of huperzine A against Aβ neurotoxicity. Above results may shed more light on the pharmacological mechanisms of huperzine A and provide important clues for discovering novel therapeutic strategies for AD.

Original languageEnglish (US)
Article numbere0128366
JournalPloS one
Volume10
Issue number5
DOIs
StatePublished - May 29 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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