综述与专论: 少突胶质细胞病——佩梅病的临床特点及致病机制
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作者单位:

1)北京大学第一医院儿科,北京 100034;2)国家医学儿童中心,首都医科大学,北京儿童医院神经内科,北京 100045

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首都卫生发展科研专项(2020-1-4071), 国家重点研发计划 (2016YFC1306201, 2016YFC0901505) 和UMHS-PUHSC 联合研 究所转化和临床研究项目(BMU2019JI009) 资助


Reviews and Monographs: Advances in Clinical Features and Pathogenesis of Pelizaeus-Merzbacher Disease
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Affiliation:

1)Department of Pediatrics, Peking University First Hospital, Beijing 100034, China;2)Department of Neurology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing100045, China

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This work was supported by grants from the Capital Health Research and Development of Special (2020-1-4071), National Key Research and Development Program of China (2016YFC1306201, 2016YFC0901505) and UMHS-PUHSC Joint Institute for Translational and Clinical Research (BMU2019JI009).

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    摘要:

    佩梅病(Pelizaeus-Merzbacher disease,PMD)是髓鞘形成低下性脑白质营养不良疾病中最常见的一种,其临床特点主要表现为发育落后尤其是大运动落后、眼震、肌张力低下等。其致病机制主要为脑白质髓鞘形成细胞-少突胶质细胞发生病理性改变从而导致髓鞘形成不良,相应理论基础包括以往研究中PLP1点突变通过影响PLP1/DM20寡聚体的形成,进而影响少突胶质细胞的存活,髓鞘分子结构的形成等;而PLP1重复突变则使少突胶质细胞及髓鞘脂的发育停止。近年来对细胞器互作网络(organelle interaction network,OIN)的研究进一步揭示了PLP1突变的致病机制:PLP1点突变通过影响PLP1蛋白上膜进而影响少突胶质细胞髓鞘化。PLP1重复突变则改变内质网线粒体间的连接,继而影响线粒体的形态功能等产生致病作用。目前已有相关研究表明,一些小分子化合物或药物例如胆固醇、吡拉西坦等以及基因疗法在动物体内对PMD临床症状有改善作用,其在PMD 患者体内的疗效有待进一步证实。

    Abstract:

    Pelizaeus-Merzbacher disease (PMD) is the most common disease of hypomyelination disorder. Most of the patients displayed with development delay especially motor delay, nystagmus and hypotonia, and so on. PMD is caused by the pathological changes of oligodendrocyte cell, which end up with hypomyelination disorder. Previous studies have demonstrated PLP1 point mutation affects the survival of oligodendrocytes and the formation of myelin molecular structure by affecting the formation of PLP1/DM20 oligomerization: PLP1 duplication stops oligodendrocyte and myelin development. Recent studies on organelle interaction network (OIN) have further demonstrated the pathogenic mechanism of PLP1 mutations: point mutations impact oligodendrocyte myelination by affecting the trafficking of PLP1 mutants to the plasma membrane. While PLP1 duplication had closer ER-mitochondrion interfaces named mitochondria-associated membranes (MAMs). These changes in both the ER and mitochondria then led to mitochondrial dysfunction. At present, relevant studies have shown that some small molecular compounds or drugs such as cholesterol, piracetam and gene therapy can improve the clinical symptoms of PMD in animals, and their efficacy in PMD patients needs to be further confirmed.

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段若愚,延会芳,王静敏.综述与专论: 少突胶质细胞病——佩梅病的临床特点及致病机制[J].生物化学与生物物理进展,2022,49(11):2115-2129

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历史
  • 收稿日期:2022-08-10
  • 最后修改日期:2022-09-28
  • 接受日期:2022-09-28
  • 在线发布日期: 2022-11-22
  • 出版日期: 2022-11-20