Hereditary spastic paraplegia.
Hereditary spastic paraplegia.
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DOI：
10.1016/b978-0-444-64076-5.00041-7
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Blackstone, Craig
中科院分区：
文献类型：
--
作者：
Blackstone, Craig
遗传性痉挛截瘫(HSPs)是一组以明显的下肢痉挛为共同特征的异质性神经系统疾病，由皮质脊髓上运动神经元的长度依赖性轴索病变引起。热休克蛋白不仅以“纯”形式存在，而且还以“复杂”形式存在，这些形式与额外的神经学和神经外功能有关。热休克蛋白是最具遗传多样性的神经疾病之一，有70多个不同的遗传位点，其中约60个突变基因已经被发现。许多研究阐明了HSPs的分子发病机制，强调了基本细胞功能--特别是膜运输、线粒体功能、细胞器成形和生物发生、轴突运输和脂肪/胆固醇代谢--在轴突发育和维持中的重要性。令人鼓舞的是，已经为最常见的热休克蛋白确定了少数趋同的细胞致病主题，其中一些途径为未来的治疗提供了引人注目的靶点。
The hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurologic disorders with the common feature of prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. The HSPs exist not only in "pure" forms but also in "complex" forms that are associated with additional neurologic and extraneurologic features. The HSPs are among the most genetically diverse neurologic disorders, with well over 70 distinct genetic loci, for which about 60 mutated genes have already been identified. Numerous studies elucidating the molecular pathogenesis underlying HSPs have highlighted the importance of basic cellular functions - especially membrane trafficking, mitochondrial function, organelle shaping and biogenesis, axon transport, and lipid/cholesterol metabolism - in axon development and maintenance. An encouragingly small number of converging cellular pathogenic themes have been identified for the most common HSPs, and some of these pathways present compelling targets for future therapies.