Posttranslational modifications & lithium’s therapeutic effect—Potential biomarkers for clinical responses in psychiatric & neurodegenerative disorders

• Published in: Neuroscience and biobehavioral reviews Vol. 127; pp. 424 - 445
• Main Authors: Khayachi, A., Schorova, L., Alda, M., Rouleau, G.A., Milnerwood, A.J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.08.2021
• Subjects: Biomarkers; Lithium responsiveness; Neurodegenerative diseases; Neuropsychiatric disorders; Posttranslational modifications homeostasis; Biomarkers; Lithium responsiveness; Neuropsychiatric disorders; Neurodegenerative diseases; Posttranslational modifications homeostasis
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2021.05.002

•Neuropsychiatric disorders display aberrant posttranslational modifications (PTM).•Lithium - a therapeutic agent for neurodegenerative and neuropsychiatric disorders.•Outline of the links between lithium’s therapeutic mode of action and PTM homeostasis.•Posttranslational modifications as a hub for disease markers and 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.