Tags

Type your tag names separated by a space and hit enter

Lithium down-regulates tau in cultured cortical neurons: a possible mechanism of neuroprotection.
Neurosci Lett. 2008 Mar 21; 434(1):93-8.NL

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.

Authors+Show Affiliations

Unité de Neurobiologie Cellulaire, EA 3842, Homéostasie Cellulaire et Pathologies, Faculté de Médecine, Université de Limoges, 87025 Limoges, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18289787

Citation

Rametti, A, et al. "Lithium Down-regulates Tau in Cultured Cortical Neurons: a Possible Mechanism of Neuroprotection." Neuroscience Letters, vol. 434, no. 1, 2008, pp. 93-8.
Rametti A, Esclaire F, Yardin C, et al. Lithium down-regulates tau in cultured cortical neurons: a possible mechanism of neuroprotection. Neurosci Lett. 2008;434(1):93-8.
Rametti, A., Esclaire, F., Yardin, C., Cogné, N., & Terro, F. (2008). Lithium down-regulates tau in cultured cortical neurons: a possible mechanism of neuroprotection. Neuroscience Letters, 434(1), 93-8. https://doi.org/10.1016/j.neulet.2008.01.034
Rametti A, et al. Lithium Down-regulates Tau in Cultured Cortical Neurons: a Possible Mechanism of Neuroprotection. Neurosci Lett. 2008 Mar 21;434(1):93-8. PubMed PMID: 18289787.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lithium down-regulates tau in cultured cortical neurons: a possible mechanism of neuroprotection. AU - Rametti,A, AU - Esclaire,F, AU - Yardin,C, AU - Cogné,N, AU - Terro,F, Y1 - 2008/01/19/ PY - 2007/12/04/received PY - 2008/01/14/revised PY - 2008/01/16/accepted PY - 2008/2/22/pubmed PY - 2008/7/4/medline PY - 2008/2/22/entrez SP - 93 EP - 8 JF - Neuroscience letters JO - Neurosci Lett VL - 434 IS - 1 N2 - 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. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/18289787/Lithium_down_regulates_tau_in_cultured_cortical_neurons:_a_possible_mechanism_of_neuroprotection_ DB - PRIME DP - Unbound Medicine ER -