Triggering endogenous neuroprotective mechanisms in Parkinson's disease: studies with a cellular model.
Triggering endogenous neuroprotective mechanisms in Parkinson's disease: studies with a cellular model.
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DOI：
10.1007/978-3-211-45295-0_66
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发表时间：
2006
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影响因子：
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通讯作者：
M. Zigmond
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作者：
M. Zigmond
胶质细胞源性神经营养因子（GDNF）参与了帕金森病（PD）动物模型中多巴胺（DA）神经元的氧化应激保护。我们现在已经表明，GDNF也可以保护免受6-羟基多巴胺（6-OHDA）的影响，在多巴胺能细胞系和培养的原代DA神经元制备的大鼠黑质（SN）。这似乎涉及细胞外信号调节激酶（ERK）的几种亚型的磷酸化的快速和瞬时增加。我们的证据表明，ERK激活也可以调制的活性氧（ROS），包括那些产生的内源性DA。识别这些途径可以被触发的方式应该提供洞察PD的病理生理学，并可能提供有用的途径，延缓疾病的进展。
Glial cell line-derived neurotrophic factor (GDNF) has been implicated in the protection of dopamine (DA) neurons from oxidative stress in animal models of Parkinson’s disease (PD). We have now shown that GDNF can also protect against the effects of 6-hydroxydopamine (6-OHDA) in a dopaminergic cell line and in cultures of primary DA neurons prepared from rat substantia nigra (SN). This appears to involve a rapid and transient increase in the phosphorylation of several isoforms of extracellular signal-regulated kinase (ERK). Our evidence indicates that ERK activation also can be modulated by reactive oxygen species (ROS), including those generated by endogenous DA. Identification of the ways by which these pathways can be triggered should provide insights into the pathophysiology of PD, and may offer useful avenues for retarding the progression of the disorder.