期刊
GROWTH FACTORS
卷 30, 期 4, 页码 242-257出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/08977194.2012.691478
关键词
Glial cell line-derived neurotrophic factor (GDNF); brain ischemia; neuroprotection; Ret receptors; NCAM
资金
- Fundacao para a Ciencia e a Tecnologia
- FEDER, Portugal [PTDC/SAU-NEU/104297/2008, PTDC/SAU-NMC/120144/2010]
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-NEU/104297/2008, PTDC/SAU-NMC/120144/2010] Funding Source: FCT
The glial cell line-derived neurotrophic factor (GDNF) was first identified as a survival factor for midbrain dopaminergic neurons, but additional studies provided evidences for a role as a trophic factor for other neurons of the central and peripheral nervous systems. GDNF regulates cellular activity through interaction with glycosyl-phosphatidylinositol-anchored cell surface receptors, GDNF family receptor-alpha 1, which might signal through the transmembrane Ret tyrosine receptors or the neural cell adhesion molecule, to promote cell survival, neurite outgrowth, and synaptogenesis. The neuroprotective effect of exogenous GDNF has been shown in different experimental models of focal and global brain ischemia, by local administration of the trophic factor, using viral vectors carrying the GDNF gene and by transplantation of GDNF-expressing cells. These different strategies and the mechanisms contributing to neuroprotection by GDNF are discussed in this review. Importantly, neuroprotection by GDNF was observed even when administered after the ischemic injury.
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