Department of Clinical Biochemistry and Pharmacology and Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev and Mental Health Center, Beer-Sheva 8461166, Israel.
Int J Mol Sci. 2020 Dec 27;22(1):189. doi: 10.3390/ijms22010189.
Lithium is the prototype mood-stabilizer used for acute and long-term treatment of bipolar disorder. Cumulated translational research of lithium indicated the drug's neuroprotective characteristics and, thereby, has raised the option of repurposing it as a drug for neurodegenerative diseases. Lithium's neuroprotective properties rely on its modulation of homeostatic mechanisms such as inflammation, mitochondrial function, oxidative stress, autophagy, and apoptosis. This myriad of intracellular responses are, possibly, consequences of the drug's inhibition of the enzymes inositol-monophosphatase (IMPase) and glycogen-synthase-kinase (GSK)-3. Here we review lithium's neurobiological properties as evidenced by its neurotrophic and neuroprotective properties, as well as translational studies in cells in culture, in animal models of Alzheimer's disease (AD) and in patients, discussing the rationale for the drug's use in the treatment of AD.
锂是一种用于治疗双相情感障碍的急性和长期治疗的典型心境稳定剂。锂的累积转化研究表明，该药物具有神经保护特性，从而提高了将其重新用作神经退行性疾病药物的可能性。锂的神经保护特性依赖于其对炎症、线粒体功能、氧化应激、自噬和细胞凋亡等稳态机制的调节。这些众多的细胞内反应可能是药物抑制肌醇单磷酸酶 (IMPase) 和糖原合酶激酶-3 (GSK-3) 的结果。在这里，我们通过其神经营养和神经保护特性以及细胞培养、阿尔茨海默病 (AD) 动物模型和患者中的转化研究来回顾锂的神经生物学特性，讨论该药物在 AD 治疗中的应用原理。
