The Neurobiological Role of Lithium Salts

Lithium salts have been the mainstay of treatment for bipolar disorder for more than 50 years, since approval by the FDA in 1970 for the treatment of this pathology. A variety of the molecular mechanisms of action of lithium have been well studied, primarily inhibition of the enzymes glycogen synthase 3β and inositol monophosphatase, with subsequent activation of cascades of cellular reactions, including induction of brain-derived neurotrophic factor and antiapoptotic proteins and suppression of calcium-dependent activation of apoptosis. Research over the last decade has focused on the effects of lithium on the regulation of autophagy and the accumulation of pathological proteins such as amyloid β and tau protein in neurons. Lithium is also thought to induce telomere elongation and to increase telomerase activity. Clinical studies of lithium have addressed the potential for its use for the prevention and treatment of neurodegenerative diseases, primarily Alzheimer’s disease, with increasing emphasis on the use of lithium microdoses. A separate scientific problem is the search for safe and effective lithium salts using methods including chemoreactome analysis.