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Systems Biology Understanding of the Effects of Lithium on Affective and Neurodegenerative Disorders.

ABSTRACT: Lithium has many widely varying biochemical and phenomenological effects, suggesting that a systems biology approach is required to understand its action. Multiple lines of evidence point to lithium intake and consequent blood levels as important determinants of incidence of neurodegenerative disease, showing that understanding lithium action is of high importance. In this paper we undertake first steps toward a systems approach by analyzing mutual enrichment between the interactomes of lithium-sensitive enzymes and the pathways associated with affective and neurodegenerative disorders. This work integrates information from two important databases, STRING and KEGG pathways. We find that for the majority of neurodegenerative disorders the mutual enrichment is many times greater than chance, reinforcing previous lines of evidence that lithium is an important influence on incidence of neurodegeneration. Our work suggests rational prioritization for which disorders are likely to be most sensitive to lithium and identifies genes that are likely to be useful targets for therapy adjunct to lithium.

SUBMITTER: Ge W

PROVIDER: S-EPMC6300566 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Systems Biology Understanding of the Effects of Lithium on Affective and Neurodegenerative Disorders.

Ge Weihao W Jakobsson Eric E

Frontiers in neuroscience 20181213

Lithium has many widely varying biochemical and phenomenological effects, suggesting that a systems biology approach is required to understand its action. Multiple lines of evidence point to lithium intake and consequent blood levels as important determinants of incidence of neurodegenerative disease, showing that understanding lithium action is of high importance. In this paper we undertake first steps toward a systems approach by analyzing mutual enrichment between the interactomes of lithium- ...[more]

PMID: 30618562

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Project description:Lithium has literally been everywhere forever, since it is one of the three elements created in the Big Bang. Lithium concentration in rocks, soil, and fresh water is highly variable from place to place, and has varied widely in specific regions over evolutionary and geologic time. The biological effects of lithium are many and varied. Based on experiments in which animals are deprived of lithium, lithium is an essential nutrient. At the other extreme, at lithium ingestion sufficient to raise blood concentration significantly over 1 mM/, lithium is acutely toxic. There is no consensus regarding optimum levels of lithium intake for populations or individuals-with the single exception that lithium is a generally accepted first-line therapy for bipolar disorder, and specific dosage guidelines for sufferers of that condition are generally agreed on. Epidemiological evidence correlating various markers of social dysfunction and disease vs. lithium level in drinking water suggest benefits of moderately elevated lithium compared to average levels of lithium intake. In contrast to other biologically significant ions, lithium is unusual in not having its concentration in fluids of multicellular animals closely regulated. For hydrogen ions, sodium ions, potassium ions, calcium ions, chloride ions, and magnesium ions, blood and extracellular fluid concentrations are closely and necessarily regulated by systems of highly selective channels, and primary and secondary active transporters. Lithium, while having strong biological activity, is tolerated over body fluid concentrations ranging over many orders of magnitude. The lack of biological regulation of lithium appears due to lack of lithium-specific binding sites and selectivity filters. Rather lithium exerts its myriad physiological and biochemical effects by competing for macromolecular sites that are relatively specific for other cations, most especially for sodium and magnesium. This review will consider what is known about the nature of this competition and suggest using and extending this knowledge towards the goal of a unified understanding of lithium in biology and the application of that understanding in medicine and nutrition.

Dataset Information

Systems Biology Understanding of the Effects of Lithium on Affective and Neurodegenerative Disorders.

Publications

Systems Biology Understanding of the Effects of Lithium on Affective and Neurodegenerative Disorders.

Similar Datasets

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