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Neuroprotective action of lithium in disorders of the central nervous system

中南大学学报（医学版） 2011年第6期36卷 461-475页

作者： Chi-Tso CHIU de-maw chuang Section on Molecular Neurobiology National Institute of Mental HealthNational Institutes of Health

Substantial in vitro and in vivo evidence of neurotrophic and neuroprotective effects of lithium suggests that it may also have considerable potential for the treatment of neurodegenerative conditions.Lithium's main mechanisms of action appear to stem from its ability to inhibit glycogen synthase kinase-3 activity and also to induce signaling mediated by brain-derived neurotrophic factor.This in turn alters a wide variety of downstream effectors,with the ultimate effect of enhancing pathways to cell survival.In addition,lithium contributes to calcium homeostasis.By inhibiting N-methyl-D-aspartate receptor-mediated calcium influx,for instance,it suppresses the calcium-dependent activation of pro-apoptotic signaling pathways.By inhibiting the activity of phosphoinositol phosphatases,it decreases levels of inositol 1,4,5-trisphosphate,a process recently identified as a novel mechanism for inducing autophagy.These mechanisms allow therapeutic doses of lithium to protect neuronal cells from diverse insults that would otherwise lead to massive cell death.Lithium,moreover,has been shown to improve behavioral and cognitive deficits in animal models of neurodegenerative diseases,including stroke,amyotrophic lateral sclerosis,fragile X syndrome,and Huntington's,Alzheimer's,and Parkinson's diseases.Since lithium is already FDA-approved for the treatment of bipolar disorder,our conclusions support the notion that its clinical relevance can be expanded to include the treatment of several neurological and neurodegenerative-related diseases.

关键词：《中南大学学报:医学版》期刊摘要编辑部

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Neuroprotection against apoptosis: what has it got to do with lithium, a mood stabilizing drug

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Cell Research 2002年第Z1期12卷 300-300页

作者： de maw chuang USA of Health Molecular Neurobiology Section National Institute of Mental Health National Institutes Bethesda MD

Lithium was introduced into psychiatry half a century ago and remains as a preferred treatment for acute mania and the preferred prophylactic therapy for manic-depressive illness. despite lithium’s standing as one of the most important drugs for neuropsychiatric disorders, the therapeutic mechanisms of this monovalent cation remain to be defined. Recent research suggests that multiple sites, rather than a single target, contribute to lithium’s mood stabilizing effects. In searching for novel actions of this drug, we found that lithium has robust neuroprotective effects, particularly against excitotoxicity.We found that lithium treatment robustly protects cultured CNS neurons from glutamate- induced

关键词： MCAO NMDA Neuroprotection against apoptosis a mood stabilizing drug what has it got to do with lithium Bax QA

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