Glutamate receptors in neuroinflammatory demyelinating disease.
Glutamate receptors in neuroinflammatory demyelinating disease.
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神经炎症性脱髓鞘性疾病中的谷氨酸受体。
DOI：
10.1155/mi/2006/93684
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发表时间：
2006
影响因子：
4.6
通讯作者：
Paul, Carolyn
中科院分区：
文献类型：
--
作者：
Bolton, Christopher;Paul, Carolyn
多发性硬化（MS）是一种中枢神经系统慢性脱髓鞘疾病。这种疾病主要影响年轻人，其特征是外周和CNS的免疫和炎症变化，导致神经血管破坏、造血细胞侵入靶组织和神经纤维脱髓鞘，最终导致复发和缓解或进行性的神经功能缺损。MS的主要特征可以在可诱导的动物对应物实验性自身免疫性脑脊髓炎（EAE）中再现。寻找新的MS治疗方法总是使用EAE来确定药物活性，并为探索临床疗效提供理论依据。用于MS的化合物的临床前开发通常遵循常规的免疫途径。然而，在过去的十年中，出现了一组抑制EAE但没有明显免疫调节活性的化合物。这些药物与谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）和α-氨基-3-羟基-5-异恶唑丙酸（AMPA）/红藻氨酸盐家族相互作用，据报道可控制神经血管通透性、炎症介质合成和神经胶质细胞功能（包括CNS髓鞘形成）。该综述考虑了谷氨酸受体在EAE和MS发病机制中的重要性。使用受体拮抗剂控制EAE也讨论了脱髓鞘疾病的治疗应用的可能性。
Multiple sclerosis (MS) is a chronic demyelinating disease of the human central nervous system (CNS). The condition predominantly affects young adults and is characterised by immunological and inflammatory changes in the periphery and CNS that contribute to neurovascular disruption, haemopoietic cell invasion of target tissues, and demyelination of nerve fibres which culminate in neurological deficits that relapse and remit or are progressive. The main features of MS can be reproduced in the inducible animal counterpart, experimental autoimmune encephalomyelitis (EAE). The search for new MS treatments invariably employs EAE to determine drug activity and provide a rationale for exploring clinical efficacy. The preclinical development of compounds for MS has generally followed a conventional, immunotherapeutic route. However, over the past decade, a group of compounds that suppress EAE but have no apparent immunomodulatory activity have emerged. These drugs interact with the N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-isoxazolepropionic acid (AMPA)/kainate family of glutamate receptors reported to control neurovascular permeability, inflammatory mediator synthesis, and resident glial cell functions including CNS myelination. The review considers the importance of the glutamate receptors in EAE and MS pathogenesis. The use of receptor antagonists to control EAE is also discussed together with the possibility of therapeutic application in demyelinating disease.