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Neuroprotective action of lithium in disorders of the central nervous system.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011 Jun; 36(6):461-76.ZN

Abstract

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.

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Authors+Show Affiliations

Chiu CT
Section on Molecular Neurobiology, National Institute of Mental Health, National Institutes of Health, 10 Center Drive MSC 1363, Bethesda, MD 20892-1363, USA.
Chuang DM
No affiliation info available

MeSH

AnimalsCentral Nervous System DiseasesHumansLithiumNeurodegenerative DiseasesNeuroprotective AgentsNootropic Agents

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural
Review

Language

eng

PubMed ID

21743136

Citation

Chiu, Chi-Tso, and De-Maw Chuang. "Neuroprotective Action of Lithium in Disorders of the Central Nervous System." Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences, vol. 36, no. 6, 2011, pp. 461-76.
Chiu CT, Chuang DM. Neuroprotective action of lithium in disorders of the central nervous system. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011;36(6):461-76.
Chiu, C. T., & Chuang, D. M. (2011). Neuroprotective action of lithium in disorders of the central nervous system. Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences, 36(6), 461-76. https://doi.org/10.3969/j.issn.1672-7347.2011.06.001
Chiu CT, Chuang DM. Neuroprotective Action of Lithium in Disorders of the Central Nervous System. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011;36(6):461-76. PubMed PMID: 21743136.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective action of lithium in disorders of the central nervous system. AU - Chiu,Chi-Tso, AU - Chuang,De-Maw, PY - 2011/7/12/entrez PY - 2011/7/12/pubmed PY - 2012/9/7/medline SP - 461 EP - 76 JF - Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences JO - Zhong Nan Da Xue Xue Bao Yi Xue Ban VL - 36 IS - 6 N2 - 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. SN - 1672-7347 UR - https://www.unboundmedicine.com/medline/citation/21743136/Neuroprotective_action_of_lithium_in_disorders_of_the_central_nervous_system_ L2 - http://xbyxb.csu.edu.cn/xbwk/fileup/PDF/201106461.pdf DB - PRIME DP - Unbound Medicine ER -