Cytosolic phospholipase A2 plays a key role in the pathogenesis of multiple sclerosis-like disease
Cytosolic phospholipase A2 plays a key role in the pathogenesis of multiple sclerosis-like disease
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DOI：
10.1016/s0896-6273(04)00003-0
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发表时间：
2004-02-05
期刊：
影响因子：
16.2
通讯作者：
David, S
中科院分区：
文献类型：
--
作者：
Kalyvas, A;David, S
多发性硬化症 (MS) 是一种中枢神经系统 (CNS) 炎症性脱髓鞘疾病，会导致运动和感觉缺陷。尽管多发性硬化症及其动物模型实验性自身免疫性脑脊髓炎 (EAE) 被认为是 T 细胞介导的疾病，但中枢神经系统病变的机制尚不完全清楚。我们认为，胞质磷脂酶 A(2) (cPLA(2)) 是引起 MS 和 EAE 中复杂病理变化的一个强有力的候选者。该酶的代谢产物之一是促炎性的，而另一种则诱导髓磷脂分解、脱髓鞘和趋化因子/细胞因子表达。我们提供的证据表明，cPLA(2) 在 EAE 病变中高表达，并表明阻断该酶可显着减少 EAE 的发病和进展。
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that results in motor and sensory deficits. Although MS and its animal model, experimental autoimmune encephalomyelitis (EAE), are thought to be T cell-mediated diseases, the mechanisms underlying the lesions in the CNS are not fully understood. We propose that a strong candidate as a central mediator in evoking the complex pathological changes seen in MS and EAE is the enzyme cytosolic phospholipase A(2) (cPLA(2)). One of the metabolic products of this enzyme is proinflammatory, while the other induces myelin breakdown, demyelination, and chemokine/cytokine expression. We provide evidence that cPLA(2) is highly expressed in EAE lesions and show that blocking this enzyme leads to a remarkable reduction in the onset and progression of EAE.