Arias-Carrión Oscar, Freundlieb Nils, Oertel Wolfgang H, Höglinger Günter U
Experimental Neurology, Philipps University, D-35033 Marburg, Germany.
CNS Neurol Disord Drug Targets. 2007 Oct;6(5):326-35. doi: 10.2174/187152707783220875.
Parkinson's disease is a neurodegenerative disorder characterized by a progressive neuronal loss affecting preferentially the dopaminergic neurons of the nigrostriatal projection. Transplantation of fetal dopaminergic precursor cells has provided the proof of principle that a cell replacement therapy can ameliorate clinical symptoms in affected patients. Recent years have provided evidence for the existence of neural stem cells with the potential to produce new neurons, particularly of a dopaminergic phenotype, in the adult mammalian brain. Such stem cells have been identified in so called neurogenic brain areas, where neurogenesis is constitutively ongoing, but also in primarily non-neurogenic areas, such as the midbrain and the striatum, where neurogenesis does not occur under normal physiological conditions. We review here presently published evidence to evaluate the concept that endogenous neural stem cells may have the potential to be instrumentalized for a non-invasive cell replacement therapy with autologous neurons to repair the damaged nigrostriatal dopaminergic projection in Parkinson's disease.
帕金森病是一种神经退行性疾病,其特征是神经元进行性丧失,主要影响黑质纹状体投射的多巴胺能神经元。胎儿多巴胺能前体细胞移植已证明细胞替代疗法可改善受影响患者的临床症状这一原理。近年来的研究证据表明,成年哺乳动物大脑中存在具有产生新神经元潜力的神经干细胞,尤其是具有多巴胺能表型的神经元。这种干细胞已在所谓的神经发生性脑区被鉴定出来,在这些区域神经发生持续存在,但也在主要非神经发生区域,如中脑和纹状体中被发现,在正常生理条件下这些区域不会发生神经发生。我们在此回顾目前已发表的证据,以评估内源性神经干细胞可能具有用于非侵入性自体神经元细胞替代疗法来修复帕金森病中受损黑质纹状体多巴胺能投射的潜力这一概念。