PDF(Pubmed)
Abstract：
Spinocerebellar ataxia type 3 (SCA3) is the most common type of disease related to poly-glutamine (polyQ) repeats. Its hallmark pathology is related to the abnormal accumulation of ataxin 3 with a longer polyQ tract (polyQ-ATXN3). However, there are other mechanisms related to SCA3 progression that require identifying trait and state biomarkers for a more accurate diagnosis and prognosis. Moreover, the identification of potential pharmacodynamic targets and assessment of therapeutic efficacy necessitates valid biomarker profiles. The aim of this review was to identify potential trait and state biomarkers and their potential value in clinical trials. Our results show that, in SCA3, there are different fluid biomarkers involved in neurodegeneration, oxidative stress, metabolism, miRNA and novel genes. However, neurofilament light chain NfL and polyQ-ATXN3 stand out as the most prevalent in body fluids and SCA3 stages. A heterogeneity analysis of NfL revealed that it may be a valuable state biomarker, particularly when measured in plasma. Nonetheless, since it could be a more beneficial approach to tracking SCA3 progression and clinical trial efficacy, it is more convenient to perform a biomarker profile evaluation than to rely on only one.
摘要：
脊髓小脑共济失调3型（SCA3）是与聚谷氨酰胺（polyQ）重复相关的最常见的疾病类型。其标志性病理学与具有较长polyQ束（polyQ-ATXN3）的共济失调蛋白3的异常积累有关。然而,还有其他与SCA3进展相关的机制,需要确定性状和状态生物标志物,以实现更准确的诊断和预后.此外，潜在药效学靶标的鉴定和治疗效果的评估需要有效的生物标志物谱.这篇综述的目的是确定潜在的性状和状态生物标志物及其在临床试验中的潜在价值。我们的研究结果表明,在SCA3中，有不同的流体生物标志物参与神经变性，氧化应激，新陈代谢，miRNA和新基因。然而,神经丝轻链NfL和polyQ-ATXN3在体液和SCA3阶段最普遍。对NfL的异质性分析表明，它可能是一种有价值的状态生物标志物，特别是在血浆中测量时。尽管如此，因为它可能是跟踪SCA3进展和临床试验疗效的更有益的方法，进行生物标志物谱评估比只依赖一个更方便.
