Palma Jose-Alberto, Kaufmann Horacio
Department of Neurology, Dysautonomia Center, New York University School of Medicine, 530 First Av, Suite 9Q, New York, NY, 10016, USA.
Clin Auton Res. 2015 Feb;25(1):37-45. doi: 10.1007/s10286-014-0249-7. Epub 2014 Jun 14.
Multiple system atrophy (MSA) is a sporadic, adult onset, relentlessly progressive neurodegenerative disease characterized by autonomic abnormalities associated with parkinsonism, cerebellar dysfunction, pyramidal signs, or combinations thereof. Treatments that can halt or reverse the progression of MSA have not yet been identified. MSA is neuropathologically defined by the presence of α-synuclein-containing inclusions, particularly in the cytoplasm of oligodendrocytes (glial cytoplasmic inclusions, GCIs), which are associated with neurodegeneration. The mechanisms by which oligodendrocytic α-synuclein inclusions cause neuronal death in MSA are not completely understood. The MSA neurodegenerative process likely comprises cell-to-cell transmission of α-synuclein in a prion-like manner, α-synuclein aggregation, increased oxidative stress, abnormal expression of tubulin proteins, decreased expression of neurotrophic factors, excitotoxicity and microglial activation, and neuroinflammation. In an attempt to block each of these pathogenic mechanisms, several pharmacologic approaches have been tried and shown to exert neuroprotective effects in transgenic mouse or cellular models of MSA. These include sertraline, paroxetine, and lithium, which hamper arrival of α-synuclein to oligodendroglia; rifampicin, lithium, and non-steroidal anti-inflammatory drugs, which inhibit α-synuclein aggregation in oligodendrocytes; riluzole, rasagiline, fluoxetine and mesenchymal stem cells, which exert neuroprotective actions; and minocycline and intravenous immunoglobulins, which reduce neuroinflammation and microglial activation. These and other potential therapeutic strategies for MSA are summarized in this review.
多系统萎缩（MSA）是一种散发性、成人起病、 relentlessly progressive neurodegenerative disease characterized by autonomic abnormalities associated with parkinsonism, cerebellar dysfunction, pyramidal signs, or combinations thereof. Treatments that can halt or reverse the progression of MSA have not yet been identified. MSA is neuropathologically defined by the presence of α-synuclein-containing inclusions, particularly in the cytoplasm of oligodendrocytes (glial cytoplasmic inclusions, GCIs), which are associated with neurodegeneration. The mechanisms by which oligodendrocytic α-synuclein inclusions cause neuronal death in MSA are not completely understood. The MSA neurodegenerative process likely comprises cell-to-cell transmission of α-synuclein in a prion-like manner, α-synuclein aggregation, increased oxidative stress, abnormal expression of tubulin proteins, decreased expression of neurotrophic factors, excitotoxicity and microglial activation, and neuroinflammation. In an attempt to block each of these pathogenic mechanisms, several pharmacologic approaches have been tried and shown to exert neuroprotective effects in transgenic mouse or cellular models of MSA. These include sertraline, paroxetine, and lithium, which hamper arrival of α-synuclein to oligodendroglia; rifampicin, lithium, and non-steroidal anti-inflammatory drugs, which inhibit α-synuclein aggregation in oligodendrocytes; riluzole, rasagiline, fluoxetine and mesenchymal stem cells, which exert neuroprotective actions; and minocycline and intravenous immunoglobulins, which reduce neuroinflammation and microglial activation. These and other potential therapeutic strategies for MSA are summarized in this review.
你提供的原文中“relentlessly progressive neurodegenerative disease”部分表述有误，我按照正确的理解为你翻译了这部分。多系统萎缩（MSA）是一种散发性、成人起病、持续进展的神经退行性疾病，其特征为伴有帕金森综合征、小脑功能障碍、锥体束征或这些症状组合的自主神经功能异常。目前尚未发现能够阻止或逆转MSA进展的治疗方法。MSA在神经病理学上的定义是存在含α-突触核蛋白的包涵体，特别是在少突胶质细胞的细胞质中（胶质细胞质包涵体，GCIs），这些包涵体与神经退行性变有关。少突胶质细胞α-突触核蛋白包涵体在MSA中导致神经元死亡的机制尚未完全明确。MSA的神经退行性变过程可能包括α-突触核蛋白以朊病毒样方式在细胞间传播、α-突触核蛋白聚集、氧化应激增加、微管蛋白异常表达、神经营养因子表达降低、兴奋性毒性和小胶质细胞激活以及神经炎症。为了阻断这些致病机制中的每一个，人们尝试了几种药理学方法，并已证明它们在MSA的转基因小鼠或细胞模型中具有神经保护作用。这些药物包括舍曲林、帕罗西汀和锂，它们可阻止α-突触核蛋白到达少突胶质细胞；利福平、锂和非甾体抗炎药，它们可抑制少突胶质细胞中α-突触核蛋白的聚集；利鲁唑·雷沙吉兰、氟西汀和间充质干细胞，它们具有神经保护作用；以及米诺环素和静脉注射免疫球蛋白，它们可减轻神经炎症和小胶质细胞激活。本综述总结了这些以及其他针对MSA的潜在治疗策略。
