Open AccessPotential Mechanisms Involved in the Prevention of Neurodegenerative Diseases by Lithium
Author(s) -
Camins Antoni,
Verdaguer Ester,
Junyent Felix,
YesteVelasco Marc,
Pelegrí Carme,
Vilaplana Jordi,
Pallás Mercé
Publication year - 2009
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/j.1755-5949.2009.00086.x
Subject(s) - neuroprotection , lithium (medication) , gsk 3 , neuroscience , mechanism (biology) , neurodegeneration , glutamate receptor , mechanism of action , pharmacology , drug discovery , disease , medicine , bioinformatics , kinase , biology , receptor , biochemistry , psychiatry , philosophy , epistemology , in vitro
Lithium is a monovalent cation that was introduced in 1949 by John Cade for the treatment of bipolar disorder. Clinical reports and subsequent studies confirmed this application and the beneficial effects of this compound. However, over the last 15 years, various authors have also demonstrated the neuroprotective effects of lithium against several neurotoxic paradigms. Thus, experimental studies in neuronal cell cultures and animal models of Alzheimer disease and others pathologies have provided strong evidence for the potential benefits of lithium. The main mechanism underlying its neuroprotective effects is thought to be inhibition of glycogen synthase kinase‐3 (GSK‐3), although other biochemical pathways in the brain could also be affected. In this review, the main mechanisms of lithium action are summarized, including the modulation of glutamate receptors, effects on arachidonic acid metabolism, its role with respect to AKT, and other potential mechanisms. In addition, its effects on neuroprotective proteins such as Bcl‐2 and p53 are also discussed. Although the cellular and molecular biological effects of lithium may constitute an effective therapeutic strategy for Alzheimer disease, further clinical and experimental studies with this drug and specific GSK‐3 inhibitors are necessary to confirm the use of lithium in therapeutic approaches to neurodegenerative diseases.