Shaltiel Galit, Chen Guang, Manji Husseini K
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-4405, USA.
Curr Opin Pharmacol. 2007 Feb;7(1):22-6. doi: 10.1016/j.coph.2006.07.005. Epub 2006 Oct 19.
Increasing evidence suggests that bipolar disorder (BPD) is associated with regional brain volumetric reductions, accompanied by cellular atrophy and/or loss. Considerable data suggest that the protypical drugs for BPD--lithium and valproate--when administered in therapeutically relevant paradigms regulate neurotrophic signaling cascades. Notably, brain-derived neurotrophic factor, the extracellular signal-regulated kinase pathway, the glycogen synthase kinase-3-mediated pathway and Bcl-2 are major targets for mood stabilizers. Further data suggest that agents which directly target neurotrophic signaling cascades may have considerable utility for the treatment of this devastating illness.
越来越多的证据表明，双相情感障碍（BPD）与脑区体积减小有关，伴有细胞萎缩和/或丢失。大量数据表明，BPD的典型药物——锂盐和丙戊酸盐——在治疗相关模式下给药时可调节神经营养信号级联反应。值得注意的是，脑源性神经营养因子、细胞外信号调节激酶通路、糖原合酶激酶-3介导的通路和Bcl-2是心境稳定剂的主要靶点。进一步的数据表明，直接靶向神经营养信号级联反应的药物可能对治疗这种毁灭性疾病具有相当大的效用。
