Prokineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration.
Prokineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration.
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DOI：
10.1038/ncomms12932
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发表时间：
2016-10-05
影响因子：
16.6
通讯作者：
Kanthasamy, Arthi
中科院分区：
文献类型：
--
作者：
Gordon, Richard;Neal, Matthew L.;Luo, Jie;Langley, Monica R.;Harischandra, Dilshan S.;Panicker, Nikhil;Charli, Adhithiya;Jin, Huajun;Anantharam, Vellareddy;Woodruff, Trent M.;Zhou, Qun-Yong;Kanthasamy, Anumantha G.;Kanthasamy, Arthi
促动素-2 （Prokineticin-2, PK2）是最近发现的一种分泌蛋白，在中枢神经系统中调节重要的生理功能，包括嗅觉生物发生和昼夜节律。有趣的是，尽管PK2在神经系统中表达较低，但其受体在黑质纹状体神经元上组成性表达。本研究表明，在多种帕金森病（PD）模型中，包括PK2报告小鼠和MitoPark小鼠，PK2的表达在退化的早期阶段在黑质多巴胺能神经元中高度诱导。功能研究表明，PK2促进线粒体生物发生，激活ERK和Akt存活信号通路，从而推动神经保护。重要的是，PK2过表达具有保护作用，而PK2受体拮抗剂会加剧实验性PD患者的多巴胺能变性。此外，PD脑存活的黑质多巴胺能神经元中PK2表达增加，表明PK2上调与人类PD临床相关。总的来说，我们的研究结果确定了代偿性神经保护PK2信号在黑质多巴胺能神经元中的范例，这可能对PD具有重要的治疗意义。促运动素-2 （PK2）是一种参与许多生理功能的分泌蛋白。在这里，作者发现PK2在帕金森病患者存活的DA神经元中表达增加，并表明它可以防止PD小鼠模型中的多巴胺能变性。
Prokineticin-2 (PK2), a recently discovered secreted protein, regulates important physiological functions including olfactory biogenesis and circadian rhythms in the CNS. Interestingly, although PK2 expression is low in the nigral system, its receptors are constitutively expressed on nigrostriatal neurons. Herein, we demonstrate that PK2 expression is highly induced in nigral dopaminergic neurons during early stages of degeneration in multiple models of Parkinson's disease (PD), including PK2 reporter mice and MitoPark mice. Functional studies demonstrate that PK2 promotes mitochondrial biogenesis and activates ERK and Akt survival signalling pathways, thereby driving neuroprotection. Importantly, PK2 overexpression is protective whereas PK2 receptor antagonism exacerbates dopaminergic degeneration in experimental PD. Furthermore, PK2 expression increased in surviving nigral dopaminergic neurons from PD brains, indicating that PK2 upregulation is clinically relevant to human PD. Collectively, our results identify a paradigm for compensatory neuroprotective PK2 signalling in nigral dopaminergic neurons that could have important therapeutic implications for PD. Prokineticin-2 (PK2) is a secreted protein involved in a number of physiological functions. Here, the authors find that PK2 expression increases in surviving DA neurons from Parkinson's disease patients, and show it protects against dopaminergic degeneration in PD mouse models.
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影响因子：
64.8
作者：
Cheng, MY;Bullock, CM;Zhou, QY
通讯作者：
Zhou, QY
影响因子：
4.8
作者：
Ghosh, Anamitra;Saminathan, Hariharan;Kanthasamy, Anumantha G.
通讯作者：
Kanthasamy, Anumantha G.
影响因子：
3.8
作者：
De Miranda, Briana R.;Popichak, Katriana A.;Tjalkens, Ronald B.
通讯作者：
Tjalkens, Ronald B.
影响因子：
3.7
作者：
Curtis VF;Wang H;Yang P;McLendon RE;Li X;Zhou QY;Wang XF
通讯作者：
Wang XF
DOI：
10.1073/pnas.0407697101
发表时间：
2004-11-30
影响因子：
11.1
作者：
LeCouter, J;Zlot, C;Ferrara, N
通讯作者：
Ferrara, N