Khalaf Guy, Mattern Claudia, Begou Mélina, Boespflug-Tanguy Odile, Massaad Charbel, Massaad-Massade Liliane
U1195 Diseases and Hormones of the Nervous System, INSERM and Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France.
M&P Pharma, Schynweg 7, 6376 Emmetten, Switzerland.
Biomedicines. 2022 Jul 15;10(7):1709. doi: 10.3390/biomedicines10071709.
Pelizaeus-Merzbacher Disease (PMD) is an inherited leukodystrophy affecting the central nervous system (CNS)-a rare disorder that especially concerns males. Its estimated prevalence is 1.45-1.9 per 100,000 individuals in the general population. Patients affected by PMD exhibit a drastic reduction or absence of myelin sheaths in the white matter areas of the CNS. The Proteolipid Protein 1 () gene encodes a transmembrane proteolipid protein. PLP1 is the major protein of myelin, and it plays a key role in the compaction, stabilization, and maintenance of myelin sheaths. Its function is predominant in oligodendrocyte development and axonal survival. Mutations in the gene cause the development of a wide continuum spectrum of leukopathies from the most severe form of PMD for whom patients exhibit severe CNS hypomyelination to the relatively mild late-onset type 2 spastic paraplegia, leading to the concept of PLP1-related disorders. The genetic diversity and the biochemical complexity, along with other aspects of PMD, are discussed to reveal the obstacles that hinder the development of treatments. This review aims to provide a clinical and mechanistic overview of this spectrum of rare diseases.
佩利措伊斯-梅茨巴赫病（PMD）是一种影响中枢神经系统（CNS）的遗传性脑白质营养不良症，这是一种罕见疾病，尤其多见于男性。据估计，普通人群中其患病率为每10万人中有1.45至1.9人。受PMD影响的患者在中枢神经系统白质区域表现出髓鞘急剧减少或缺失。蛋白脂质蛋白1（PLP1）基因编码一种跨膜蛋白脂质蛋白。PLP1是髓鞘的主要蛋白质，在髓鞘的压实、稳定和维持中起关键作用。其功能在少突胶质细胞发育和轴突存活中占主导地位。PLP1基因突变会导致一系列广泛的白质病变，从最严重的PMD形式（患者表现出严重的中枢神经系统髓鞘发育不全）到相对较轻的迟发性2型痉挛性截瘫，从而引出了PLP1相关疾病的概念。本文讨论了PMD的遗传多样性、生化复杂性以及其他方面，以揭示阻碍治疗发展的障碍。本综述旨在提供这一系列罕见疾病的临床和机制概述。
