Vollum Institute, Oregon Health and Science University Portland, OR, USA ; Department of Neurology, Oregon Health and Science University Portland, OR, USA.
Front Physiol. 2013 Jul 25;4:169. doi: 10.3389/fphys.2013.00169. eCollection 2013.
Multiple sclerosis (MS) has traditionally been considered an autoimmune inflammatory disorder leading to demyelination and clinical debilitation as evidenced by our current standard anti-inflammatory and immunosuppressive treatment regimens. While these approaches do control the frequency of clinical relapses, they do not prevent the progressive functional decline that plagues many people with MS. Many avenues of research indicate that a neurodegenerative process may also play a significant role in MS from the early stages of disease, and one of the current hypotheses identifies mitochondrial dysfunction as a key contributing mechanism. We have hypothesized that pathological permeability transition pore (PTP) opening mediated by reactive oxygen species (ROS) and calcium dysregulation is central to mitochondrial dysfunction and neurodegeneration in MS. This focused review highlights recent evidence supporting this hypothesis, with particular emphasis on our in vitro and in vivo work with the mitochondria-targeted redox enzyme p66ShcA.
多发性硬化症（MS）传统上被认为是一种自身免疫性炎症性疾病，导致脱髓鞘和临床虚弱，这可以从我们目前的标准抗炎和免疫抑制治疗方案中得到证明。虽然这些方法确实可以控制临床复发的频率，但它们并不能防止困扰许多 MS 患者的进行性功能下降。许多研究途径表明，神经退行性过程也可能在疾病的早期阶段在 MS 中发挥重要作用，目前的一个假设将线粒体功能障碍确定为关键的致病机制。我们假设，由活性氧（ROS）和钙失调介导的病理性通透性转换孔（PTP）开放是 MS 中线粒体功能障碍和神经退行性变的核心。这篇重点综述强调了支持这一假设的最新证据，特别强调了我们在体外和体内使用线粒体靶向氧化还原酶 p66ShcA 的工作。
