Lithium Effects on Neurodegenerative Diseases

Lithium, traditionally employed as a mood stabiliser, has garnered considerable attention for its neuroprotective properties across a spectrum of neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Huntington’s diseases. Experimental and clinical studies indicate that lithium exerts multifaceted actions: it inhibits key enzymes such as glycogen synthase kinase-3, modulates inositol signalling, enhances autophagy and supports mitochondrial function. These effects converge to reduce amyloid-β accumulation, diminish tau phosphorylation, attenuate neuroinflammation and oxidative stress, and promote neurogenesis and synaptic plasticity. The narrow therapeutic window of lithium has spurred development of novel formulations and microdose regimens aimed at maximising neuroprotective efficacy while minimising adverse effects on renal and thyroid function. Emerging evidence from preclinical models and early‐phase clinical trials suggests that strategically timed lithium treatment can stabilise cognitive decline and modify disease progression, underscoring its potential as an affordable, disease-modifying therapy in an ageing population for which few effective treatments exist.

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Lithium Effects on Neurodegenerative Diseases publication trend

The graph below shows the total number of articles in lithium effects on neurodegenerative diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Glycogen synthase kinase-3 (GSK-3): A serine/threonine kinase whose inhibition by lithium reduces tau phosphorylation and regulates multiple survival pathways.

Autophagy: The cellular process of degrading and recycling damaged organelles and protein aggregates to maintain neuronal health.

Neurogenesis: The generation of new neurons in regions such as the hippocampus, contributing to learning and memory.

Synaptic plasticity: The ability of synapses to strengthen or weaken over time, essential for cognitive function.

Amyloid-β: Peptides that aggregate extracellularly to form plaques, a hallmark of Alzheimer’s disease pathology.

Tau phosphorylation: The addition of phosphate groups to tau protein, which promotes formation of neurofibrillary tangles in Alzheimer’s disease.

References

1. Molecular mechanisms and therapeutic potential of lithium in Alzheimer’s disease: repurposing an old class of drugs. Frontiers in Pharmacology (2024).
2. Is There Justification to Treat Neurodegenerative Disorders by Repurposing Drugs? The Case of Alzheimer’s Disease, Lithium, and Autophagy. International Journal of Molecular Sciences (2020).
3. Neuronal–Glial Interaction in a Triple-Transgenic Mouse Model of Alzheimer’s Disease: Gene Ontology and Lithium Pathways. Frontiers in Neuroscience (2020).