Tsai Shih-Jen
Department of Psychiatry, Taipei Veterans General Hospital, No. 201 Shih-Pai Road, Sec. 2, 11217 Taipei, Taiwan
Med Hypotheses. 2007;69(6):1219-21. doi: 10.1016/j.mehy.2007.04.014. Epub 2007 Jun 4.
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. The hallmark pathologic feature of PD is dopamine deficiency, caused by the degeneration of nigrostriatal dopaminergic neurons. Current treatments for PD mainly address the dopaminergic features of the disease; however they do not modify the progression of neurodegeneration. The need for newer and more effective agents is consequently receiving a great deal of attention. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, can promote survival of injured dopaminergic nigrostriatal neurons in the rodent. Postmortem studies have suggested that BDNF deficiency may play a role in PD pathogenesis. This is further supported by the finding that BDNF administration has a therapeutic effect in animal models of PD. Glatiramer acetate (GA) is a collection of synthetic polypeptides approved for the treatment of relapsing-remitting multiple sclerosis. Preclinical studies have demonstrated that peripheral GA administration can enhance central BDNF activity and augment neurogenesis. Furthermore, PD has been associated with an inflammatory process in the brain. Animal studies have demonstrated that GA administration has a central anti-inflammatory effect through the release of anti-inflammatory cytokines. From the above evidence, GA could act as a potential therapeutic agent for PD by increasing central BDNF and by exerting an anti-inflammatory effect. With the recent finding that GA administration can prevent neuronal loss and cognitive decline in Alzheimer's disease double-transgenic mice, early GA treatment may also prevent neurodegeneration and manifestations of PD symptoms in subjects with familial Parkinson's disease.
帕金森病（PD）是仅次于阿尔茨海默病的第二常见神经退行性疾病。PD的标志性病理特征是多巴胺缺乏，这是由黑质纹状体多巴胺能神经元变性引起的。目前PD的治疗主要针对该疾病的多巴胺能特征；然而，它们并不能改变神经退行性变的进程。因此，对更新、更有效药物的需求受到了广泛关注。脑源性神经营养因子（BDNF）是神经营养因子家族的一员，可促进啮齿动物中受损多巴胺能黑质纹状体神经元的存活。尸检研究表明，BDNF缺乏可能在PD发病机制中起作用。BDNF给药在PD动物模型中具有治疗作用这一发现进一步支持了这一点。醋酸格拉替雷（GA）是一组被批准用于治疗复发缓解型多发性硬化症的合成多肽。临床前研究表明，外周给予GA可增强中枢BDNF活性并促进神经发生。此外，PD与大脑中的炎症过程有关。动物研究表明，给予GA可通过释放抗炎细胞因子产生中枢抗炎作用。基于上述证据，GA可能通过增加中枢BDNF并发挥抗炎作用而成为PD的潜在治疗药物。随着最近发现给予GA可预防阿尔茨海默病双转基因小鼠的神经元丢失和认知衰退，早期给予GA治疗也可能预防家族性帕金森病患者的神经退行性变和PD症状表现。
