The Wld(S) mutation delays anterograde, but not retrograde, axonal degeneration of the dopaminergic nigro-striatal pathway in vivo.
The Wld(S) mutation delays anterograde, but not retrograde, axonal degeneration of the dopaminergic nigro-striatal pathway in vivo.
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DOI：
10.1111/j.1471-4159.2010.06632.x
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发表时间：
2010-05
影响因子：
4.7
通讯作者：
Burke RE
中科院分区：
文献类型：
--
作者：
Cheng HC;Burke RE
对于许多神经退行性疾病，如帕金森病，有证据表明，这种疾病首先影响选择性脆弱的神经元的轴突和末梢。这表明，通过靶向轴突变性的细胞机制来阻止进展是可能的。虽然现在很清楚这些机制与程序性细胞死亡的途径不同，但它们鲜为人知。这些机制的独特性的令人信服的证据来自于WldS突变的研究，该突变赋予轴突变性的抗性。关于这种突变如何影响多巴胺能轴突的变性，人们知之甚少，这些轴突在帕金森病中受到影响。我们的特点是在这些轴突的WldS表型在四个模型的损伤：两个利用神经毒素6-羟基多巴胺或轴突切断诱导顺行变性，和两个使用这些方法来诱导逆行变性。对于6-羟基多巴胺和轴突切断术，WldS提供了顺行性保护，但不是逆行性变性。这种保护被观察为保留轴突和纹状体中的酪氨酸羟化酶的免疫染色，并通过酪氨酸羟化酶-GFP小鼠中的GFP可视化的结构完整性。因此，WldS提供轴突保护，但它揭示了根本不同的过程，在这个系统中的前变性和逆行变性。
For many neurodegenerative disorders, such as Parkinson’s disease, there is evidence that the disease first affects axons and terminals of neurons that are selectively vulnerable. This would suggest that it may be possible to forestall progression by targeting the cellular mechanisms of axon degeneration. While it is now clear that these mechanisms are distinct from the pathways of programmed cell death, they are less well known. Compelling evidence of the distinctiveness of these mechanisms has derived from studies of the WldS mutation, which confers resistance to axon degeneration. Little is known about how this mutation affects degeneration in dopaminergic axons, those that are affected in Parkinson’s disease. We have characterized the WldS phenotype in these axons in four models of injury: two that utilize the neurotoxin 6-hydroxydopamine or axotomy to induce anterograde degeneration, and two that use these methods to induce retrograde degeneration. For both 6-hydroxydopamine and axotomy, WldS provides protection from anterograde, but not retrograde degeneration. This protection is observed as preserved immunostaining for tyrosine hydroxylase in axons and striatum, and by structural integrity visualized by GFP in tyrosine hydroxylase-GFP mice. Therefore, WldS offers axon protection, but it reveals fundamentally different processes underlying antero- and retrograde degeneration in this system.
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影响因子：
25
作者：
Li, Yanping;Liu, Wencheng;Oo, Tinmarla F.;Wang, Lei;Tang, Yi;Jackson-Lewis, Vernice;Zhou, Chun;Geghman, Kindiya;Bogdanov, Mikhail;Przedborski, Serge;Beal, M. Flint;Burke, Robert E.;Li, Chenjian
通讯作者：
Li, Chenjian
影响因子：
25
作者：
Mack, TGA;Reiner, M;Coleman, MP
通讯作者：
Coleman, MP
影响因子：
5.3
作者：
Hasbani, Daphne M.;O'Malley, Karen L.
通讯作者：
O'Malley, Karen L.
影响因子：
3.4
作者：
LUNN, ER;PERRY, VH;GORDON, S
通讯作者：
GORDON, S
DOI：
10.1006/neur.1995.0016
发表时间：
1995-06-01
期刊：
NEURODEGENERATION
影响因子：
--
作者：
JEON, BS;JACKSONLEWIS, V;BURKE, RE
通讯作者：
BURKE, RE