Lithium and neuroprotection: translational evidence and implications for the treatment of neuropsychiatric disorders

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art_MACHADO-VIEIRA_Lithium_and_neuroprotection_translational_evidence_and_implications_for_2013.PDF (488.66 KB)
Citações na Scopus
70
Tipo de produção
article
Data de publicação
2013
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
DOVE MEDICAL PRESS LTD
Autores
DINIZ, Breno Satler
Citação
NEUROPSYCHIATRIC DISEASE AND TREATMENT, v.9, p.493-500, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
In the last two decades, a growing body of evidence has shown that lithium has several neuroprotective effects. Several neurobiological mechanisms have been proposed to underlie these clinical effects. Evidence from preclinical studies suggests that neuroprotection induced by lithium is mainly related to its potent inhibition of the enzyme glycogen synthase kinase-3 beta (GSK-3 beta) and its downstream effects, ie, reduction of both tau protein phosphorylation and amyloid-beta(42) production. Additional neuroprotective effects include increased neurotrophic support, reduced proinflammatory status, and decreased oxidative stress. More recently, neuroimaging studies in humans have demonstrated that chronic use is associated with cortical thickening, higher volume of the hippocampus and amygdala, and neuronal viability in bipolar patients on lithium treatment. In line with this evidence, observational and case registry studies have shown that chronic lithium intake is associated with a reduced risk of Alzheimer's disease in subjects with bipolar disorder. Evidence from recent clinical trials in patients with mild cognitive impairment suggests that chronic lithium treatment at subtherapeutic doses can reduce cerebral spinal fluid phosphorylated tau protein. Overall, convergent lines of evidence point to the potential of lithium as an agent with disease modifying properties in Alzheimer's disease. However, additional long-term studies are necessary to confirm its efficacy and safety for these patients, particularly as chronic intake is necessary to achieve the best therapeutic results.
Palavras-chave
lithium, Alzheimer's disease, prevention, GSK-3 beta, neuroprotection
URI
https://observatorio.fm.usp.br/handle/OPI/2144
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPS
Artigos e Materiais de Revistas Científicas - LIM/27