Choi-Lundberg D L, Lin Q, Chang Y N, Chiang Y L, Hay C M, Mohajeri H, Davidson B L, Bohn M C
Department of Neurobiology and Anatomy, University of Rochester, Box 603, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Science. 1997 Feb 7;275(5301):838-41. doi: 10.1126/science.275.5301.838.
Glial cell line-derived neurotrophic factor (GDNF) supports growth and survival of dopaminergic (DA) neurons. A replication-defective adenoviral (Ad) vector encoding human GDNF injected near the rat substantia nigra was found to protect DA neurons from the progressive degeneration induced by the neurotoxin 6-hydroxydopamine (6-OHDA) injected into the striatum. Ad GDNF gene therapy reduced loss of DA neurons approximately threefold 6 weeks after 6-OHDA lesion, as compared with no treatment or injection of Ad lacZ or Ad mGDNF (encoding a biologically inactive deletion mutant GDNF). These results suggest that Ad vector-mediated GDNF gene therapy may slow the DA neuronal cell loss in humans with Parkinson's disease.
胶质细胞源性神经营养因子（GDNF）可支持多巴胺能（DA）神经元的生长和存活。研究发现，将编码人GDNF的复制缺陷型腺病毒（Ad）载体注射到大鼠黑质附近，可保护DA神经元免受注入纹状体内的神经毒素6-羟基多巴胺（6-OHDA）所诱导的进行性退变。与未治疗或注射Ad lacZ或Ad mGDNF（编码无生物学活性的缺失突变体GDNF）相比，Ad GDNF基因治疗在6-OHDA损伤6周后使DA神经元损失减少了约三倍。这些结果表明，Ad载体介导的GDNF基因治疗可能会减缓帕金森病患者DA神经元的细胞损失。
