Walker D G, Beach T G, Xu R, Lile J, Beck K D, McGeer E G, McGeer P L
Kinsmen Laboratory of Neurological Research and Neurodegenerative Disease Centre, University of British Columbia, Vancouver, BC, Canada.
Brain Res. 1998 May 11;792(2):207-17. doi: 10.1016/s0006-8993(98)00131-0.
The proto-oncogene Ret, a membrane-associated receptor protein tyrosine kinase, has recently been shown to be a component of the glial cell line-derived neurotrophic factor (GDNF) receptor complex. GDNF has potent dopaminergic neurotrophic properties and has been suggested as a treatment for Parkinson's disease (PD). In this study, tissue sections of human substantia nigra (SN) from normal and PD cases were examined to determine the pattern of Ret expression in this region, and whether there was continued Ret expression in surviving dopaminergic neurons in PD cases. Using a polyclonal antibody to the amino terminal of Ret, immunoreactivity was localized in the SN to dopaminergic neurons. The antibody predominantly identified punctate deposits within cells. A similar pattern of immunoreactivity was observed in rat and monkey SN neurons. In neurologically normal cases, immunoreactivity was detected in many of the SN neurons. In all the PD cases studied, continued expression of Ret was observed in many of the surviving dopaminergic neurons. In certain cases, it was also detected on cells with the morphology of microglia. Ret expression by microglia was confirmed by immunoblot analysis on the human THP-1 macrophage type cell line. However, these cells did not express the mRNA for GDNFRalpha, the other component of the GDNF receptor complex.
原癌基因Ret是一种膜相关受体蛋白酪氨酸激酶，最近已被证明是胶质细胞源性神经营养因子（GDNF）受体复合物的一个组成部分。GDNF具有强大的多巴胺能神经营养特性，并已被建议用于治疗帕金森病（PD）。在本研究中，对来自正常和PD病例的人类黑质（SN）组织切片进行检查，以确定该区域Ret的表达模式，以及PD病例中存活的多巴胺能神经元是否持续表达Ret。使用针对Ret氨基末端的多克隆抗体，免疫反应性在SN中定位于多巴胺能神经元。该抗体主要识别细胞内的点状沉积物。在大鼠和猴子的SN神经元中观察到类似的免疫反应模式。在神经功能正常的病例中，在许多SN神经元中检测到免疫反应性。在所有研究的PD病例中，在许多存活的多巴胺能神经元中观察到Ret的持续表达。在某些情况下，在具有小胶质细胞形态的细胞上也检测到了Ret。通过对人THP-1巨噬细胞系进行免疫印迹分析，证实了小胶质细胞表达Ret。然而，这些细胞不表达GDNF受体复合物的另一个组成部分GDNFRα的mRNA。
