PDF(Pubmed)
Abstract：
Over the last six decades, lithium has been considered the gold standard treatment for the long-term management of bipolar disorder due to its efficacy in preventing both manic and depressive episodes as well as suicidal behaviors. Nevertheless, despite numerous observed effects on various cellular pathways and biologic systems, the precise mechanism through which lithium stabilizes mood remains elusive. Furthermore, there is recent support for the therapeutic potential of lithium in other brain diseases. This review offers a comprehensive examination of contemporary understanding and predominant theories concerning the diverse mechanisms underlying lithium\'s effects. These findings are based on investigations utilizing cellular and animal models of neurodegenerative and psychiatric disorders. Recent studies have provided additional support for the significance of glycogen synthase kinase-3 (GSK3) inhibition as a crucial mechanism. Furthermore, research has shed more light on the interconnections between GSK3-mediated neuroprotective, antioxidant, and neuroplasticity processes. Moreover, recent advancements in animal and human models have provided valuable insights into how lithium-induced modifications at the homeostatic synaptic plasticity level may play a pivotal role in its clinical effectiveness. We focused on findings from translational studies suggesting that lithium may interface with microRNA expression. Finally, we are exploring the repurposing potential of lithium beyond bipolar disorder. These recent findings on the therapeutic mechanisms of lithium have provided important clues toward developing predictive models of response to lithium treatment and identifying new biologic targets. SIGNIFICANCE STATEMENT: Lithium is the drug of choice for the treatment of bipolar disorder, but its mechanism of action in stabilizing mood remains elusive. This review presents the latest evidence on lithium\'s various mechanisms of action. Recent evidence has strengthened glycogen synthase kinase-3 (GSK3) inhibition, changes at the level of homeostatic synaptic plasticity, and regulation of microRNA expression as key mechanisms, providing an intriguing perspective that may help bridge the mechanistic gap between molecular functions and its clinical efficacy as a mood stabilizer.
摘要：
在过去的六十年里，由于锂在预防躁狂和抑郁发作以及自杀行为方面的功效，因此被认为是双相情感障碍长期治疗的金标准治疗方法。然而，尽管对各种细胞途径和生物系统有许多观察到的影响，锂稳定情绪的确切机制仍然难以捉摸。此外，最近有人支持锂在其他脑部疾病中的治疗潜力。这篇综述全面考察了当代关于锂效应的各种机制的理解和主要理论。这些发现基于利用神经退行性疾病和精神疾病的细胞和动物模型的研究。最近的研究为糖原合酶激酶3（GSK3）抑制作为关键机制的重要性提供了额外的支持。此外，研究已经揭示了GSK3介导的神经保护之间的相互联系，抗氧化剂，和神经可塑性过程。此外，动物和人体模型的最新进展为锂诱导的稳态突触可塑性水平的修饰如何在其临床有效性中起关键作用提供了有价值的见解。我们专注于翻译研究的发现，表明锂可能与microRNA表达有关。最后,我们正在探索锂在双相情感障碍之外的再利用潜力。这些关于锂治疗机制的最新发现为开发锂治疗反应的预测模型和确定新的生物靶标提供了重要线索。意义声明：锂是双相情感障碍治疗的首选药物，但是它在稳定情绪方面的作用机制仍然难以捉摸。这篇综述提供了锂的各种作用机制的最新证据。最近的证据加强了糖原合成酶激酶-3（GSK3）的抑制，稳态突触可塑性水平的变化，和调节microRNA表达的关键机制，提供了一个有趣的观点，这可能有助于弥合分子功能与其作为情绪稳定剂的临床疗效之间的机制差距。
