Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca 50180, Mexico.
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Int J Mol Sci. 2024 Jul 24;25(15):8074. doi: 10.3390/ijms25158074.
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.
脊髓小脑共济失调 3 型（SCA3）是最常见的与多聚谷氨酰胺（polyQ）重复相关的疾病类型。其标志性病理学与更长的多聚谷氨酰胺重复的共济失调蛋白 3（polyQ-ATXN3）的异常积累有关。然而，SCA3 进展还涉及其他机制，需要确定特征和状态生物标志物，以进行更准确的诊断和预后。此外，鉴定潜在的药效学靶点和评估治疗效果需要有效的生物标志物谱。本综述的目的是确定潜在的特征和状态生物标志物及其在临床试验中的潜在价值。我们的结果表明，在 SCA3 中，有不同的与神经退行性变、氧化应激、代谢、miRNA 和新基因相关的液体生物标志物。然而，神经丝轻链 NfL 和 polyQ-ATXN3 在体液和 SCA3 阶段最为常见。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，由于它可能是跟踪 SCA3 进展和临床试验效果的更有益方法，因此进行生物标志物谱评估比仅依赖一种生物标志物更为方便。
