Is There Justification to Treat Neurodegenerative Disorders by Repurposing Drugs? The Case of Alzheimer's Disease, Lithium, and Autophagy

Lithium is the prototype mood-stabilizer used for acute and long-term treatment of bipolar disorder. Cumulated translational research of lithium indicated the drug's neuroprotective characteristics and, thereby, has raised the option of repurposing it as a drug for neurodegenerative diseases. Lithium's neuroprotective properties rely on its modulation of homeostatic mechanisms such as inflammation, mitochondrial function, oxidative stress, autophagy, and apoptosis. This myriad of intracellular responses are, possibly, consequences of the drug's inhibition of the enzymes inositol-monophosphatase (IMPase) and glycogen-synthase-kinase (GSK)-3. Here we review lithium's neurobiological properties as evidenced by its neurotrophic and neuroprotective properties, as well as translational studies in cells in culture, in animal models of Alzheimer's disease (AD) and in patients, discussing the rationale for the drug's use in the treatment of AD.

Automated summary

Lithium, a prototype mood stabilizer, is being considered for repurposing as a drug for neurodegenerative diseases due to its neuroprotective properties. Its mechanism of action involves modulation of homeostatic mechanisms and inhibition of enzymes such as IMPase and GSK-3, resulting in a range of intracellular responses. Studies in cells, animal models, and patients have shown promise for the use of lithium in the treatment of Alzheimer's disease.