The Genetics and Pathophysiology of Spinocerebellar Degeneration

随着人口老龄化，脊髓小脑性共济失调（SCA）是一个越来越重要的问题，具有潜伏的进展和没有特定的治疗。据估计，英国成年人非获得性共济失调的患病率为10,000人（数据来自英国共济失调）。这种神经退行性疾病是选择性的和进行性的，引起小脑的神经元损失，这定义了临床和病理图像。已知遗传因素使小脑神经元易受细胞死亡的影响，但大量这些因素尚未确定。特别是对共济失调的常见危险因素和疾病调节剂了解甚少。利用已建立的基因组方法、小脑表达技术、细胞培养模型和神经病理学研究，我们将确定导致脊髓小脑变性的疾病过程和途径。了解这些生物过程将有助于形成一个通路网络来研究共济失调的环境原因，允许开发抑制或逆转疾病过程的治疗方法，并精确地描述临床试验的患者特征。

With an ageing population, spinocerebellar ataxia (SCA) is an increasingly important problem with insidious progression and no specific treatment. The estimated prevalence in adults of non-acquired ataxia in the UK is 10,000 people (data from ataxia UK). This neurodegenerative disorder is selective and progressive causing neuronal loss in the cerebellum which defines the clinical and pathological picture. Genetic factors are known to render cerebellar neurons vulnerable to cell death but a large number of these factors are yet to be identified. In particular the common risk factors and disease modifiers of ataxia are poorly understood.Using established genomic methods, cerebellar expression techniques, cell culture models and neuropathological investigations we will identify the disease processes and pathways that lead to spinocerebellar degeneration. Understanding these biological processes will help form a network of pathways to investigate environmental causes of ataxia, allow the development of treatments to inhibit or reverse the disease process and precisely characterise patients for clinical trials.