Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia.
Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia.
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DOI：
10.18632/aging.100358
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Gallouzi IE
中科院分区：
文献类型：
--
作者：
Hall DT;Ma JF;Marco SD;Gallouzi IE
肌肉萎缩-也称为肌肉萎缩-是一种使人衰弱的综合征，随着年龄的增长而缓慢发展（肌肉减少症）或在致命疾病如癌症，艾滋病和败血症（恶病质）的晚期迅速出现。尽管这两种综合征的患病率和严重的有害影响，目前还没有广泛使用的，有效的治疗方案，为那些患有肌肉萎缩。在试图确定潜在的治疗靶点，肌肉减少症和恶病质的分子机制已开始阐明。越来越多的证据表明，炎症细胞因子可能在这两种综合征的病理学中起重要作用。肿瘤坏死因子α（tumor necrosis factor α，TNFα）及其下游效应子是引起肌肉萎缩和恶病质性肌肉萎缩的关键细胞因子之一，是药物干预的重要靶点。然而，迄今为止，没有靶向TNFα信号通路的药物成功地作为治疗肌肉萎缩的补救选择。因此，有必要确定新的效应在这一重要的途径，可能被证明是更有效的目标。诱导型一氧化氮合酶（iNOS）是TNFα诱导的恶病质性肌肉损失的重要介质，研究表明它也可能在肌肉减少症中发挥作用。此外，对iNOS介导的肌肉损失机制的研究已经开始揭示潜在的治疗策略。在这篇综述中，我们将强调潜在的针对iNOS/NO通路在治疗肌肉损失，并讨论其功能的相关性在肌肉减少症和恶病质。
Muscle atrophy—also known as muscle wasting—is a debilitating syndrome that slowly develops with age (sarcopenia) or rapidly appears at the late stages of deadly diseases such as cancer, AIDS, and sepsis (cachexia). Despite the prevalence and the drastic detrimental effects of these two syndromes, there are currently no widely used, effective treatment options for those suffering from muscle wasting. In an attempt to identify potential therapeutic targets, the molecular mechanisms of sarcopenia and cachexia have begun to be elucidated. Growing evidence suggests that inflammatory cytokines may play an important role in the pathology of both syndromes. As one of the key cytokines involved in both sarcopenic and cachectic muscle wasting, tumor necrosis factor α (TNFα) and its downstream effectors provide an enticing target for pharmacological intervention. However, to date, no drugs targeting the TNFα signaling pathway have been successful as a remedial option for the treatment of muscle wasting. Thus, there is a need to identify new effectors in this important pathway that might prove to be more efficacious targets. Inducible nitric oxide synthase (iNOS) has recently been shown to be an important mediator of TNFα-induced cachectic muscle loss, and studies suggest that it may also play a role in sarcopenia. In addition, investigations into the mechanism of iNOS-mediated muscle loss have begun to reveal potential therapeutic strategies. In this review, we will highlight the potential for targeting the iNOS/NO pathway in the treatment of muscle loss and discuss its functional relevance in sarcopenia and cachexia.
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