Luca Antonina, Calandra Carmela, Luca Maria
Department of Medical and Surgical Sciences and Advanced Technologies, University Hospital Policlinico-Vittorio Emanuele, Santa Sofia Street 78, Catania, 95100 Sicily, Italy.
Psychiatry Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University Hospital Policlinico-Vittorio Emanuele, Santa Sofia Street 78, Catania, 95100 Sicily, Italy.
Oxid Med Cell Longev. 2016;2016:3030547. doi: 10.1155/2016/3030547. Epub 2016 Aug 18.
Objective. To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned "biological causes" of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD.
目的。探讨糖原合酶激酶-3（GSK3）与双相情感障碍（BD）中表现出的主要生物学改变之间的联系，特别关注氧化还原状态以及支持锂盐（一种GSK3抑制剂）治疗BD疗效的证据。方法。利用PubMed和谷歌学术对上述主题进行了文献研究。此外，还对已识别文章中有趣的参考文献进行了人工筛选。结果。BD的主要生物学改变，涉及炎症、氧化应激、膜离子通道和昼夜节律系统，似乎相互交织。GSK3信号通路功能障碍参与了BD所有上述“生物学病因”。在一个复杂的情况下，它可被视为将它们全部联系起来的共同因素。锂盐对GSK3的抑制作用至少可以部分解释其对这些生物学功能障碍的积极作用及其在临床疗效方面的优越性。结论。深入了解BD的分子基础对于确定必须靶向的生化途径至关重要，以便为患者提供针对BD这种使人衰弱的疾病越来越有效的治疗工具。
