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亨廷顿舞蹈症和帕金森病中的生物标志物

Biomarkers in Huntington's and Parkinson's Disease.

作者信息

O'Keeffe Gráinne C, Michell Andrew W, Barker Roger A

机构信息

Cambridge Centre for Brain Repair, Department of Clinical Neuroscience, University of Cambridge, Cambridge CB2 0PY, United Kingdom.

出版信息

Ann N Y Acad Sci. 2009 Oct;1180:97-110. doi: 10.1111/j.1749-6632.2009.04943.x.

Abstract

Parkinson's (PD) and Huntington's disease (HD) are chronic neurodegenerative conditions of the brain with a variety of clinical presentations including a disorder of movement and a range of nonmotor deficits. HD is genetic in origin and the causative gene and protein known, namely mutant Huntingtin, which leads to widespread early neuronal dysfunction and death throughout the brain. In contrast, the etiology of sporadic PD is unknown, and the pathology targets the nigrostriatal dopaminergic neurons with the formation of alpha-synuclein positive Lewy bodies. In both diseases, the ability to accurately diagnose the disease in the early stages and monitor progression over time remains a major challenge given the majority of the pathology is sited deep within the CNS. This challenge has gained extra significance as the development of disease-modifying drugs starts to emerge into the clinic. To this end, there is a need to find biomarkers that will help in the accurate diagnosis of the disease and/or prediction of its clinical onset as well as biomarkers that are able to faithfully track disease progression independent of any symptomatic effects of any therapies. In addition, these same markers may also help stratify each of these heterogeneous disorders into specific subtypes that share particular clinical and pathological characteristics.

摘要

帕金森病(PD)和亨廷顿舞蹈病(HD)是脑部慢性神经退行性疾病,有多种临床表现,包括运动障碍和一系列非运动功能缺损。HD起源于遗传,致病基因和蛋白质已知,即突变型亨廷顿蛋白,它会导致全脑广泛的早期神经元功能障碍和死亡。相比之下,散发性PD的病因不明,其病理改变以黑质纹状体多巴胺能神经元为靶点,并形成α-突触核蛋白阳性的路易小体。在这两种疾病中,鉴于大多数病理改变位于中枢神经系统深处,在疾病早期准确诊断并监测疾病随时间的进展仍然是一项重大挑战。随着疾病修饰药物开始进入临床,这一挑战变得尤为重要。为此,需要找到有助于准确诊断疾病和/或预测其临床发病的生物标志物,以及能够独立于任何治疗的症状效应而忠实地追踪疾病进展的生物标志物。此外,这些相同的标志物还可能有助于将这些异质性疾病中的每一种分为具有特定临床和病理特征的特定亚型。

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