Liedewei Van de Vondel, Jonathan De Winter, Vincent Timmerman, Jonathan Baets
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引用次数: 0
摘要
国际罕见病遗传学合作联盟极大地促进了我们对遗传性神经系统疾病的了解。遗传性周围神经病(IPNs)、痉挛性截瘫和小脑性共济失调等病因看似不同的疾病之间划定了历史性的临床分类界限。由于基因突变显示出广泛的表型谱和共同的病理机制主题,这些临床定义的边界正受到挑战,而这些主题是开发疗法的宝贵指征。我们重点介绍了这种遗传格局背后的常见细胞改变,包括细胞骨架、轴突运输、线粒体功能和 DNA 修复反应的改变。最后,我们讨论了未来研究的方向,即以前瞻性神经系统长轴突病变为模型,探索其他神经遗传性疾病。
Overarching pathomechanisms in inherited peripheral neuropathies, spastic paraplegias, and cerebellar ataxias.
International consortia collaborating on the genetics of rare diseases have significantly boosted our understanding of inherited neurological disorders. Historical clinical classification boundaries were drawn between disorders with seemingly different etiologies, such as inherited peripheral neuropathies (IPNs), spastic paraplegias, and cerebellar ataxias. These clinically defined borders are being challenged by the identification of mutations in genes displaying wide phenotypic spectra and by shared pathomechanistic themes, which are valuable indications for therapy development. We highlight common cellular alterations that underlie this genetic landscape, including alteration of cytoskeleton, axonal transport, mitochondrial function, and DNA repair response. Finally, we discuss venues for future research using the long axonopathies of the PNS as a model to explore other neurogenetic disorders.
期刊介绍:
For over four decades, Trends in Neurosciences (TINS) has been a prominent source of inspiring reviews and commentaries across all disciplines of neuroscience. TINS is a monthly, peer-reviewed journal, and its articles are curated by the Editor and authored by leading researchers in their respective fields. The journal communicates exciting advances in brain research, serves as a voice for the global neuroscience community, and highlights the contribution of neuroscientific research to medicine and society.