Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India.
Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, 226 001, Uttar Pradesh, India.
Neurotox Res. 2019 Oct;36(3):627-644. doi: 10.1007/s12640-019-00080-4. Epub 2019 Jul 2.
Devastating motor features, lack of early prognostic tools, and absence of undeviating therapies call for an endeavor to develop biomarkers for Parkinson's disease (PD). A biomarker is anticipated to help in timely and selective diagnosis as well as to hunt for an appropriate treatment option. Peripheral fingerprints can be used to assess the progression, distinguish PD from other related disorders, and monitor the efficacy of therapeutic options. From the last two decades, peripheral blood is constantly targeted in search of an appropriate marker owing to minimal invasive procedure for collection, highly dynamic nature, and insignificant ethical concern. Besides, cerebrospinal fluid (CSF) is also preferred because of its close proximity to the brain. Employing conventional and contemporary sophisticated devices, a number of protein and non-protein entities, mainly metallic elements, have been shown to hold adequate potential to be used as biomarkers for monitoring progression and assessing treatment options for such a distressing neurodegenerative disorder. Classical strategies and relatively newer sophisticated tools, such as proteomics, deciphered the presence of an altered level of highly specific blood- and CSF-specific proteins, free metals, metal-binding proteins, common inflammatory proteins, and overexpressed/modified α-synuclein in PD patients. While several chemical entities are shown to be associated, not even a single protein or metal is converted into unambiguous disease fingerprint. The article provides an update on proteins and metals that are shown to possess enormous potential in the course of biomarker exploration but are unable to deliver a reliable indicator. The review also sheds light on the reasons of ineffective hit to hunt for an authentic fingerprint and proposes the doable ways to translate the output into reality.
毁灭性的运动特征、缺乏早期预后工具以及缺乏明确的治疗方法，这一切都要求我们努力寻找帕金森病（PD）的生物标志物。生物标志物有望帮助进行及时和有针对性的诊断，并寻找合适的治疗选择。外周指纹可以用于评估疾病进展、区分 PD 与其他相关疾病，并监测治疗选择的效果。在过去的二十年中，由于采集过程微创、性质高度动态以及伦理关注较小，外周血一直是寻找合适标志物的目标。此外，由于其与大脑的密切关系，脑脊液（CSF）也被优先考虑。采用传统和现代的复杂设备，已经发现许多蛋白质和非蛋白质实体，主要是金属元素，具有足够的潜力作为生物标志物，用于监测疾病进展和评估这种令人痛苦的神经退行性疾病的治疗选择。经典策略和相对较新的复杂工具，如蛋白质组学，揭示了 PD 患者血液和 CSF 中特定蛋白质、游离金属、金属结合蛋白、常见炎症蛋白和过度表达/修饰的α-突触核蛋白水平发生改变。虽然有几种化学实体被证明与疾病相关，但没有一种蛋白质或金属被转化为明确的疾病指纹。本文提供了关于蛋白质和金属的最新信息，这些物质在生物标志物探索过程中显示出巨大的潜力，但无法提供可靠的指标。该综述还探讨了未能找到可靠的生物标志物的原因，并提出了将研究成果转化为实际应用的可行方法。
