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Lithium down-regulates tau in cultured cortical neurons: a possible mechanism of neuroprotection.

Abstract : In tauopathies such as Alzheimer's disease (AD), the moleccular mechanisms of tau protein agregation into neurofibrillary tangles (NFTs) and their contribution to neurodegeneration are not fully understood. Recent studies indirectly demonstrated that tau, regardless of its aggregation, might represent a key mediator of neurodegeneration, especially that induced by the amyloid (Abeta) pathology. Lithium is a medication for bipolar mood disorders. Its therapeutic mechanism of action remains unclear, in part because of the large number of biochemical effects attributed to lithium. Since lithium directly inhibits glycogen synthase kinase-3beta (GSK3beta), a key enzyme involved in tau phosphorylation, it was suggested that the therapeutic use of lithium could be expanded from mood disorders to neurodegenerative conditions. Lithium has been also reported to protect cultured neurons against Abeta toxicity, and to prevent NFTs accumulation and cognitive impairments in transgenic models of tauopathies. However, the exact mechanism of neuroprotection provided by lithium remains unknown. Here, we show that exposure of cultured cortical neurons to lithium decreased tau protein levels. This decrease was not linked to the activation of proteolytic processes including calpains, caspases and proteasome or to neuronal loss, but was rather associated with a reduction in tau mRNA levels. Moreover, prior exposure to lithium, at concentrations effective in reducing tau protein levels, markedly reduced pre-aggregated Abeta-induced neuronal apoptosis. Our findings raise the possibility that lithium could exert its neuroprotective effect against Abeta toxicity through the downregulation of tau proteins and that, at least, by acting at the level of tau mRNA.
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Contributeur : Claire Douady Connectez-vous pour contacter le contributeur
Soumis le : mercredi 18 mai 2011 - 16:28:17
Dernière modification le : dimanche 26 juin 2022 - 13:22:12

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Armelle Rametti, Françoise Esclaire, Catherine Yardin, Nadine Cogné, Faraj Terro. Lithium down-regulates tau in cultured cortical neurons: a possible mechanism of neuroprotection.. Neuroscience Letters, 2008, 434 (1), pp.93-8. ⟨10.1016/j.neulet.2008.01.034⟩. ⟨hal-00594077⟩



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