期刊
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
卷 127, 期 -, 页码 424-445出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neubiorev.2021.05.002
关键词
Neuropsychiatric disorders; Neurodegenerative diseases; Posttranslational modifications homeostasis; Biomarkers; Lithium responsiveness
资金
- Fonds de recherche en sante du Quebec (FRSQ)
- Killam foundation
- Canadian Institutes of Health Research (CIHR) [332971]
- ERAPerMed grant PLOT-BD
- RI-MUHC 2020 fellowship
- Ellen foundation
The effectiveness and mode of action of lithium treatment for neurological conditions remains not fully understood, although studies have shown its impact on protein posttranslational modifications and neuronal physiology. Determining specific posttranslational modification patterns could be a promising strategy to develop disease biomarkers and predict lithium responsiveness.
Several neurodegenerative diseases and neuropsychiatric disorders display aberrant posttranslational modifications (PTMs) of one, or many, proteins. Lithium treatment has been used for mood stabilization for many decades, and is highly effective for large subsets of patients with diverse neurological conditions. However, the differential effectiveness and mode of action are not fully understood. In recent years, studies have shown that lithium alters several protein PTMs, altering their function, and consequently neuronal physiology. The impetus for this review is to outline the links between lithium's therapeutic mode of action and PTM homeostasis. We first provide an overview of the principal PTMs affected by lithium. We then describe several neuropsychiatric disorders in which PTMs have been implicated as pathogenic. For each of these conditions, we discuss lithium's clinical use and explore the putative mechanism of how it restores PTM homeostasis, and thereby cellular physiology. Evidence suggests that determining specific PTM patterns could be a promising strategy to develop biomarkers for disease and lithium responsiveness.
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