Pathogenesis of Parkinson's disease - prospects of neuroprotective and restorative therapies
Pathogenesis of Parkinson's disease - prospects of neuroprotective and restorative therapies
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DOI：
10.1385/mn:29:1:15
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发表时间：
2004-02-01
影响因子：
5.1
通讯作者：
Fernandez-Espejo, E
中科院分区：
文献类型：
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作者：
Fernandez-Espejo, E
帕金森病(PD)是由黑质向纹状体投射的多巴胺能神经元变性引起的。特发性帕金森病的病因不明，大多数病例是散发性的。人们普遍认为，这种疾病有遗传因素，发病年龄越早，遗传因素起主导作用的可能性就越大。黑质的氧化应激似乎包含了神经退化的驱动力，导致了破坏性的“毒害循环”。最普遍的治疗方法是左旋多巴，但经过几年的治疗后并不有效。目前正在探索几种替代疗法，例如神经保护方法。具有潜在神经保护作用的化合物，如司来吉兰、多巴胺激动剂、利鲁唑、肌酸和辅酶Q10目前正在进行测试。营养因子代表了另一类神经保护化合物，但它们的脑内给药很难实现。在这方面，一个潜在有用的治疗方法是移植细胞载体，释放营养分子，刺激受损的黑质纹状体系统再生。利用基因工程的成纤维细胞分泌胶质细胞源性神经营养因子(GDNF)或脑源性神经营养因子(BDNF)或表达GDNF的病毒载体已取得了可喜的结果。我们已经测试了从Zuckerkandl‘s器官获得的嗜铬细胞在纹状体内移植的适宜性，这些细胞对帕金森病大鼠起到了有益的作用，并释放了营养因子，如GDNF和转化生长因子-β(1)(TGF-β(1))。
Parkinson's disease (PD) is caused by the degeneration of dopaminergic neurons of substantia nigra projecting to striatum. The cause of idiopathic PD is obscure, and most cases are sporadic. It is widely accepted that there is a genetic component of the disease, and the earlier the age of onset, the greater the likelihood that genetic factors play a dominant role. Oxidative stress of the substantia nigra seems to contain the driving force for neurodegeneration, leading to a destructive "toxic cycle." The most prevalent therapy is levodopa administration, but it is not efficacious after several years of treatment. Several alternative therapies are currently being explored, such as neuroprotective approaches. Compounds with potentially neuroprotective efficacy such as selegiline, dopamine agonists, riluzole, creatine, and coenzyme Q10 are currently being tested. Trophic factors represent another class of neuroprotective compounds, but their intracerebral administration is difficult to achieve. hi this respect, a potentially useful therapeutic approach is grafting cell vectors that release trophic molecules that stimulate regeneration in the damaged nigrostriatal system. Promising results have been obtained with fibroblasts engineered to secrete glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) or viral vectors expressing GDNF. We have tested the suitability of intrastriatal grafts of chromaffin cells obtained from the Zuckerkandl's organ, which exert beneficial effects in parkinsonian rats, and release trophic factors such as GDNF and transforming growth factor-beta(1) (TGF- beta(1)).