Adenosine signaling and function in glial cells.

Adenosine signaling and function in glial cells.
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DOI:
10.1038/cdd.2009.131
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发表时间:
2010-07
影响因子:
12.4
通讯作者:
Fredholm, B. B.
Fredholm, B. B.
中科院分区:
生物学1区
文献类型:
--
作者:
Boison, D.;Chen, J-F;Fredholm, B. B.

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尽管在各种神经科学研究领域取得了重大进展,但大多数神经退行性疾病和神经系统疾病都无法通过目前可用的药物控制,这些药物主要基于神经中心药物设计。过去五年的研究已经确立了神经胶质在确定神经元功能方面的核心作用,因此神经胶质功能障碍几乎与每一种神经退行性疾病和神经系统疾病有关。神经胶质细胞是大脑内源性神经保护剂和抗惊厥剂腺苷的关键调节剂。本文将总结胶质细胞如何促进腺苷稳态以及胶质腺苷受体如何影响胶质功能。然后,我们将继续讨论胶质细胞如何与神经元和血管系统相互作用,并概述研究胶质功能的新方法。我们将讨论神经胶质对腺苷功能的控制如何影响神经元细胞死亡及其对癫痫、创伤性脑损伤、缺血和帕金森病的影响。最终,神经胶质腺苷调节药物靶点可能成为治疗神经退行性疾病的一个有吸引力的替代方案。然而,仍有几个重大的未决问题有待解决。
Despite major advances in a variety of neuroscientific research fields, the majority of neurodegenerative and neurological diseases are poorly controlled by currently available drugs, which are largely based on a neurocentric drug design. Research from the past five years has established a central role of glia to determine how neurons function and – consequently – glial dysfunction is implicated in almost every neurodegenerative and neurological disease. Glial cells are key regulators of the brain’s endogenous neuroprotectant and anticonvulsant adenosine. This review will summarize how glial cells contribute to adenosine homeostasis and how glial adenosine receptors affect glial function. We will then move on to discuss how glial cells interact with neurons and the vasculature and outline new methods to study glial function. We will discuss how glial control of adenosine-function affects neuronal cell death and its implications for epilepsy, traumatic brain injury, ischemia, and Parkinson’s disease. Eventually, glial adenosine-modulating drug targets might be an attractive alternative for the treatment of neurodegenerative diseases. There are, however, several major open questions that remain to be tackled.
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