Truncated tau and Aβ cooperatively impair mitochondria in primary neurons

NEUROBIOLOGY OF AGING

卷:33

Article

Dolan, Philip J.^2,3  Jin, Youngnam N.²  Johnson, Gail V. W.^1,2 

[1] Univ Rochester, Dept Anesthesiol, Med Ctr, Rochester, NY 14642 USA

[2] Univ Rochester, Dept Physiol & Pharmacol, Rochester, NY 14642 USA

[3] Univ Alabama Birmingham, Dept Cell Biol, Birmingham, AL 35294 USA

关键词: Tau;    Alzheimer;    Mitochondria;    Caspase;    A beta;    Oxidative stress;   

DOI  :  10.1016/j.neurobiolaging.2011.02.007

来源: Elsevier

【 摘 要 】

Mitochondrial dysfunction is likely a significant contributing factor to Alzheimer disease pathogenesis, and both amyloid peptide (A beta) and pathological forms of tau may contribute to this impairment. Cleavage of tau at Asp421 occurs early in Alzheimer disease, and Asp421-cleaved tau likely negatively impacts neuronal function. Previously we showed that expression of Asp421-cleaved tau in a neuronal cell model resulted in mitochondrial impairment. To extend these findings we expressed either full length tau or Asp421-cleaved tau (truncated tau) in primary cortical neurons and measured different aspects of mitochondrial function with or without the addition of sublethal concentrations of A beta. The expression of truncated tau alone induced significant mitochondrial fragmentation in neurons. When truncated tau expression was combined with A beta at sublethal concentrations, increases in the stationary mitochondrial population and the levels of oxidative stress in cortical neurons were observed. Truncated tau expression also enhanced A beta-induced mitochondrial potential loss in primary neurons. These new findings show that Asp421-cleaved tau and A beta cooperate to impair mitochondria, which likely contributes to the neuronal dysfunction in Alzheimer disease. (C) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

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