. Functional mitochondria are required for amyloid beta-mediated neurotoxicity. FASEB J. 2001 Jun;15(8):1439-41. PubMed.

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  1. Mitochondria, Amyloid-β, and Metabolism

    Studies of amyloid-β (Aβ) cellular toxicity using cells with the full complement of organelles have implicated various sites of action but have primarily focused on the plasma membrane (Mark et al., 1997). Indeed, an intracellular organellar site of Aβ action seemed at variance with plasma membrane effects involving Ca2+ entry thereby relegating mitochondrial abnormalities to secondary events.

    However, in an elegant study, Cardoso and colleagues (2001) show that Aβ toxicity is strictly dependent on functional mitochondria such that Aβ has no effect on neuroblastoma cells lacking mitochondria (r0). When seen in light of the strict dependence of Ab toxicity on iron (Rottkamp et al., 2001) and altered Ab metabolism in cells populated by mitochondria from cases of Alzheimer disease (AD) (Khan et al., 2000), there appears to be a compelling case for a mitochondria-Aβ link. In fact, given that reduced brain metabolism is one of the earliest events in AD (Small et al., 2000), an important role of Aβ might be related to metabolic function. Therefore, instead of mediating toxicity, Aβ could serve to regulate metabolic state as compensation to a catastrophic disease process. - George Perry and Mark Smith, Institute of Pathology, Case Western Reserve University

    References:

    Cardoso SM, Santos S, Swerdlow RH, Oliveira CR. "Functional mitochondria are required for amyloid β-mediated neurotoxicity." FASEB J 15:1439-1441. Abstract.

    Khan SM, Cassarino DS, Abramova NN, Keeney PM, Borland MK, Trimmer PA, Krebs CT, Bennett JC, Parks JK, Swerdlow RH, Parker WD Jr, Bennett JP Jr. "Alzheimer's disease cybrids replicate β-amyloid abnormalities through cell death pathways." Ann Neurol. 48, 148-155. Abstract.

    Mark RJ, Pang Z, Geddes JW, Uchida K, Mattson MP. "Amyloid β-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipi peroxidation." J Neurosci 17, 1046-1054. Abstract.

    Rottkamp CA, Raina AK, Zhu X, Gaier E, Bush AI, Atwood CS, Chevion M, Perry G, Smith MA. "Redox-active iron mediates amyloid-β toxicity." Free Radic Biol Med 30, 447-450. Abstract.

    Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, Lavretsky H, Miller K, Siddarth P, Rasgon NL, Mazziotta JC, Saxena S, Wu HM, Mega MS, Cummings JL, Saunders AM, Pericak-Vance MA, Roses AD, Barrio JR, Phelps ME. "Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease." Proc Natl. Acad. Sci USA 97, 6037-6042. Abstract.

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