Naef Valentina, Mero Serena, Fichi Gianluca, D'Amore Angelica, Ogi Asahi, Gemignani Federica, Santorelli Filippo M, Marchese Maria
Neurobiology and Molecular Medicine, IRCCS Stella Maris, Pisa, Italy.
Department of Biology, University of Pisa, Pisa, Italy.
Front Neurosci. 2019 Dec 10;13:1311. doi: 10.3389/fnins.2019.01311. eCollection 2019.
Hereditary spastic paraplegia (HSP) and hereditary ataxia (HA) are two groups of disorders characterized, respectively, by progressive dysfunction or degeneration of the pyramidal tracts (HSP) and of the Purkinje cells and spinocerebellar tracts (HA). Although HSP and HA are generally shown to have distinct clinical-genetic profiles, in several cases the clinical presentation, the causative genes, and the cellular pathways and mechanisms involved overlap between the two forms. Genetic analyses in humans in combination with and studies using model systems have greatly expanded our knowledge of spinocerebellar degenerative disorders. In this review, we focus on the zebrafish (), a vertebrate model widely used in biomedical research since its overall nervous system organization is similar to that of humans. A critical analysis of the literature suggests that zebrafish could serve as a powerful experimental tool for molecular and genetic dissection of both HA and HSP. The zebrafish, found to be very useful for demonstrating the causal relationship between defect and mutation, also offers a useful platform to exploit for the development of therapies.
遗传性痉挛性截瘫（HSP）和遗传性共济失调（HA）是两组分别以锥体束（HSP）以及浦肯野细胞和脊髓小脑束（HA）的进行性功能障碍或退变为特征的疾病。尽管HSP和HA通常显示出不同的临床遗传特征，但在一些病例中，两种形式的临床表现、致病基因以及涉及的细胞途径和机制存在重叠。人类的遗传分析与使用模型系统的研究相结合，极大地扩展了我们对脊髓小脑退行性疾病的认识。在本综述中，我们重点关注斑马鱼（Danio rerio），由于其整体神经系统组织与人类相似，它是生物医学研究中广泛使用的脊椎动物模型。对文献的批判性分析表明，斑马鱼可作为对HA和HSP进行分子和遗传剖析的强大实验工具。斑马鱼被发现对于证明缺陷与突变之间的因果关系非常有用，它也为开发治疗方法提供了一个有用的平台。
