Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Laboratory of Neuromuscular Pathology, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Laboratory of Neuromuscular Pathology, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Neuromuscular Reference Centre, Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
Trends Neurosci. 2024 Mar;47(3):227-238. doi: 10.1016/j.tins.2024.01.004. Epub 2024 Feb 14.
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.
国际罕见病遗传学研究合作组织极大地促进了我们对遗传性神经疾病的理解。历史上，根据病因学的不同，对遗传性周围神经病（IPN）、痉挛性截瘫和小脑共济失调等疾病进行了临床分类。但是，具有广泛表型谱的基因突变的鉴定和共同的病理生理机制主题正在挑战这些临床定义的边界，这些主题为治疗开发提供了有价值的依据。我们强调了遗传景观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，我们讨论了利用周围神经的长轴突病变作为模型来探索其他神经遗传疾病的未来研究方向。
