. Annonacin, a natural mitochondrial complex I inhibitor, causes tau pathology in cultured neurons. J Neurosci. 2007 Jul 18;27(29):7827-37. PubMed.

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  1. The study by Escobar-Khondiker and colleagues again illustrates the role mitochondrial dysfunction has in disease. The authors show that annonacin, a food toxin and complex I inhibitor that has caused an endemic to Guadeloupe, causes, in striatal cultures, a redistribution of tau, retrograde transport of mitochondria, and cell death. The authors are able to show that other ATP-depleting substances cause a similar phenotype. The tau-associated pathology found in striatal neurons after annonacin treatment occurs in the absence of tau aggregation and filament formation. This suggests, again convincingly, that in tauopathies a tau pathology (with increased tau levels) can be dissociated from tau aggregate formation. In figure 9 of their paper the authors present a model of how annonacin causes ATP depletion, altered tau distribution, and microtubule breakdown. Together with our study of a mitochondrial dysfunction in P301L tau transgenic mice and in FTD (David et al., 2005), these data suggest a vicious cycle of alterations in tau levels/distribution and mitochondrial impairment in AD and related neurodegenerative diseases.

    References:

    . Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice. J Biol Chem. 2005 Jun 24;280(25):23802-14. PubMed.