Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar.
College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar.
J Neurochem. 2019 Sep;150(5):626-636. doi: 10.1111/jnc.14809. Epub 2019 Jul 28.
Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease and is estimated to affect approximately 1-4% of individuals aged over 60 years old. Although considerable efforts have been invested into developing disease-modifying therapies for Parkinson's disease, such efforts have been confounded by the difficulty in accurately diagnosing Parkinson's disease during life to enable accurate patient stratification for clinical trialling of candidate therapeutics. Therefore, the search for effective biomarkers that can be accurately evaluated during life with non-invasive means is a pressing issue in the field. Since the discovery of α-synuclein (α-syn) as a protein linked to a familial form of Parkinson's disease, later identified as the major protein component of the neuropathological hallmark of idiopathic Parkinson's disease, considerable interest has focused on this protein and its distinct conformers. We describe here the progress that has been made in the area of Parkinson's disease biomarker discovery with a focus on α-synuclein. In particular, we highlight the novel assays that have been employed and the increasing complexity in evaluating α-synuclein with regard to the considerable diversity of conformers that exist in the biofluids and peripheral tissues under disease conditions. "This article is part of the Special Issue Synuclein."
帕金森病是仅次于阿尔茨海默病的第二常见神经退行性疾病，估计影响 60 岁以上人群的 1%-4%。尽管人们投入了大量精力来开发帕金森病的疾病修饰疗法，但由于在有生之年难以准确诊断帕金森病，从而难以准确分层患者以进行候选治疗药物的临床试验，这些努力受到了阻碍。因此，寻找可通过非侵入性手段在有生之年准确评估的有效生物标志物是该领域的当务之急。自发现与家族性帕金森病相关的α-突触核蛋白（α-syn）以来，α-syn 后来被确定为特发性帕金森病神经病理学标志的主要蛋白成分，此后人们对这种蛋白及其独特构象体产生了浓厚的兴趣。我们在这里描述了在帕金森病生物标志物发现领域取得的进展，重点介绍了α-突触核蛋白。特别是，我们强调了所采用的新检测方法，并强调了在评估生物体液和疾病状态下外周组织中存在的大量构象体的α-syn 时，检测方法的日益复杂化。“本文是突触核蛋白特刊的一部分。”
