Escobar-Khondiker M, Höllerhage M, Muriel MP, Champy P, Bach A, Depienne C, Respondek G, Yamada ES, Lannuzel A, Yagi T, Hirsch EC, Oertel WH, Jacob R, Michel PP, Ruberg M, Höglinger GU. 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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The University of Queensland
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:
David DC, Hauptmann S, Scherping I, Schuessel K, Keil U, Rizzu P, Ravid R, Dröse S, Brandt U, Müller WE, Eckert A, Götz J. Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice. J Biol Chem. 2005 Jun 24;280(25):23802-14. PubMed.
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