Is lithium a universal inhibitor? Evidence arising from clinical neuroscience and oncology

Abstract

Lithium has been in the environment from the origin of life, interacting with almost all of the biological molecules that life invented. Lithium affects many components of intracellular signalling pathways, inhibiting more than ten cellular targets and displacing magnesium ions. Lithium modulates cell function via inhibitory effects on adenosine triphosphatase activity, cyclic adenosine monophosphate, and intracellular enzymes. Lithium is also an important inhibitor of the enzyme glycogen synthase kinase-3. Recent epidemiological findings strongly support the benefits of lithium use in both neuropsychiatry and oncology. Lithium is the first line drug used in the management of bipolar disorders, while natural lithium level intake may influence impulsiveness, a possible core factor mediating the manifestation of both suicidality and aggressiveness. Lithium is also useful in a broad range of diseases: neurological, such as epilepsy, Huntington chorea, Parkinson diseases, and headaches; endocrinological, such as hyperthyreosis, diabetes mellitus, and the inappropriate secretion of the antidiuretic hormone; haematological, such as neutropenia, and thrombocytopenia; and alergological, such as asthma. Moreover, lithium has been tested with promising results in oncology. Lithium reverts the apoptosis models by interfering receptor function, while a long-term lithium treatment has been shown to increase the expression of antiapoptotic genes. Lithium chloride has been also found to hold anticancer properties, while combination treatments with lithium can improve the efficacy of chemotherapeutic agents in apoptosis deficient cancer cells. Lithium can modulate autophagy in esophageal and colorectal cancer cells. A large retrospective study showed that lithium-exposed individuals were less likely to suffer melanoma-associated mortality and recent epidemiological findings showed a reduced overall cancer risk in bipolar patients treated with lithium. What we know about the effects of lithium seems to be a small fraction of what there is to know, but it seems that lithium has been central to survival in the process of biological evolution. Lithium demonstrates a broad range of inhibitory effects from the cell to the behavioral level. We may suggest that lithium operates like a natural universal inhibitor, helping the organisms to readjust balances and to survive, through the development of compensatory and readapting mechanisms.