Fractalkine Mediates Communication between Pathogenic Proteins and Microglia: Implications of Anti-Inflammatory Treatments in Different Stages of Neurodegenerative Diseases.
Fractalkine Mediates Communication between Pathogenic Proteins and Microglia: Implications of Anti-Inflammatory Treatments in Different Stages of Neurodegenerative Diseases.
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DOI：
10.1155/2012/345472
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发表时间：
2012
影响因子：
--
通讯作者：
Moussa CE
中科院分区：
文献类型：
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作者：
Desforges NM;Hebron ML;Algarzae NK;Lonskaya I;Moussa CE
炎症在神经退行性疾病中的作用已得到广泛证实。神经元内蛋白质的积累可能通过趋化因子裂解素（CX3CL1）信号通路调节小胶质细胞的活性，该通路提供了神经元与小胶质细胞相互沟通的机制。在神经退行性疾病的不同阶段以及各种动物模型中，CX3CL1水平会发生波动，这使得有必要进一步研究小胶质细胞对致病性蛋白质（包括 Tau蛋白、β - 淀粉样蛋白（Aβ）和α - 突触核蛋白）反应的潜在机制。小胶质细胞活性与致病性蛋白质定位（细胞内与细胞外）之间的时间关系可能决定神经炎症是减轻还是加剧疾病进展。转基因模型中的证据表明，小胶质细胞活性对清除像Aβ这样的蛋白质有有益作用，而对Tau蛋白的修饰有有害作用，但CX3CL1信号在α - 突触核蛋白病中的作用不太明确。在此，我们综述了趋化因子裂解素介导的神经元 - 小胶质细胞相互作用的性质，这对神经退行性病理不同阶段抗炎治疗的效果具有重要意义。具体而言，在疾病早期神经元内蛋白质积累阶段进行抗炎治疗可能是有益的，而在疾病后期当蛋白质分泌到细胞外空间时进行抗炎治疗可能会加剧疾病进展。
The role of inflammation in neurodegenerative diseases has been widely demonstrated. Intraneuronal protein accumulation may regulate microglial activity via the fractalkine (CX3CL1) signaling pathway that provides a mechanism through which neurons communicate with microglia. CX3CL1 levels fluctuate in different stages of neurodegenerative diseases and in various animal models, warranting further investigation of the mechanisms underlying microglial response to pathogenic proteins, including Tau, β-amyloid (Aβ), and α-synuclein. The temporal relationship between microglial activity and localization of pathogenic proteins (intra- versus extracellular) likely determines whether neuroinflammation mitigates or exacerbates disease progression. Evidence in transgenic models suggests a beneficial effect of microglial activity on clearance of proteins like Aβ and a detrimental effect on Tau modification, but the role of CX3CL1 signaling in α-synucleinopathies is less clear. Here we review the nature of fractalkine-mediated neuronmicroglia interaction, which has significant implications for the efficacy of anti-inflammatory treatments during different stages of neurodegenerative pathology. Specifically, it is likely that anti-inflammatory treatment in early stages of disease during intraneuronal accumulation of proteins could be beneficial, while anti-inflammatory treatment in later stages when proteins are secreted to the extracellular space could exacerbate disease progression.