P2Y(12) receptor on the verge of a neuroinflammatory breakdown.

P2Y(12) receptor on the verge of a neuroinflammatory breakdown.
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DOI:
10.1155/2014/975849
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发表时间:
2014
影响因子:
4.6
通讯作者:
Volonté C
Volonté C
中科院分区:
医学3区
文献类型:
--
作者:
Amadio S;Parisi C;Montilli C;Carrubba AS;Apolloni S;Volonté C

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在中枢神经系统,在肌萎缩侧索硬化症(ALS)和多发性硬化症(MS)等病理过程中发生的神经炎症是由各种细胞表型协调的复杂相互作用的结果。在这一过程中发挥作用的分子信号中,细胞外核苷酸负责细胞间的沟通和炎性刺激的传播。这是通过与几种受体亚型(定义为P2X/P2Y)结合发生的,这些受体亚型广泛存在于不同的组织中,并同时定位于多个细胞。例如,在中枢神经系统的小胶质细胞上、在少突胶质细胞上、在髓鞘形成中具有假想作用的星形胶质细胞上,以及在星形胶质细胞上,都发现了代谢型P2Y12亚型。通过比较分析,我们在此建立了抗C末端抗体或第二细胞内环抗体标记的P2Y12受体,在神经炎性条件下分别分布于分支小胶质细胞或有髓纤维、原代器官型小脑培养物、大鼠纹状体和小脑组织切片、症状/终末期SOD-G93A ALS小鼠脊髓切片以及进展性MS供者的身体皮质组织中。我们认为,P2Y12表达的调节可能作为分支/监控性小胶质细胞和脱髓鞘病变的双重分析标记物,因此在神经炎性条件下具有潜在的预测价值,就像在ALS和MS中发现的那样。
In the CNS, neuroinflammation occurring during pathologies as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) is the consequence of an intricate interplay orchestrated by various cell phenotypes. Among the molecular cues having a role in this process, extracellular nucleotides are responsible for intercellular communication and propagation of inflammatory stimuli. This occurs by binding to several receptor subtypes, defined P2X/P2Y, which are widespread in different tissues and simultaneously localized on multiple cells. For instance, the metabotropic P2Y12 subtype is found in the CNS on microglia, affecting activation and chemotaxis, on oligodendrocytes, possessing a hypothesized role in myelination, and on astrocytes. By comparative analysis, we have established here that P2Y12 receptor immunolabelled by antibodies against C-terminus or second intracellular loop, is, respectively, distributed and modulated under neuroinflammatory conditions on ramified microglia or myelinated fibers, in primary organotypic cerebellar cultures, tissue slices from rat striatum and cerebellum, spinal cord sections from symptomatic/end stage SOD1-G93A ALS mice, and finally autoptic cortical tissue from progressive MS donors. We suggest that modulation of P2Y12 expression might play a dual role as analytic marker of branched/surveillant microglia and demyelinating lesions, thus potentially acquiring a predictive value under neuroinflammatory conditions as those found in ALS and MS.
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