Bioinformatics and Human Electrophysiology Laboratory, Department of Informatics, Ionian University, Corfu, Greece.
Adv Exp Med Biol. 2021;1338:193-198. doi: 10.1007/978-3-030-78775-2_23.
Parkinson's disease is a gradually progressive neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the midbrain area called the substantia nigra pars compacta and cytoplasmic alpha-synuclein-rich inclusions termed Lewy bodies. The etiology and pathogenesis remain incompletely understood. The development of reliable biomarkers for the early and accurate diagnosis, including biochemical, genetic, clinical, and neuroimaging markers, is crucial for unraveling the pathogenic processes of the disease as well as patients' progress surveillance. High-throughput technologies and system biology methodologies can support the identification of potent molecular fingerprints together with the establishment of dynamic network biomarkers. Emphasis is given on multi-omics datasets and dysregulated pathways associated with differentially expressed transcripts, modified protein motifs, and altered metabolic profiles. Although there is no therapy that terminates the neurodegenerative process and dopamine replacement strategy with L-DOPA represents the most effective treatment, numerous therapeutic protocols such as dopamine receptor agonists, MAO-B inhibitors, and cholinesterase inhibitors represent candidate treatments providing at the same time valuable network-based approaches to drug repositioning. Computational methodologies and bioinformatics platforms for visualization, clustering, and validating of molecular and clinical datasets provide important insights into diagnostic processing and therapeutic pipeline.
帕金森病是一种进行性神经退行性疾病，其特征是中脑区域的多巴胺能神经元选择性丧失，称为黑质致密部的细胞浆α-突触核蛋白富含包涵体，称为路易体。其病因和发病机制仍不完全清楚。开发可靠的生物标志物对于早期和准确诊断至关重要，包括生化、遗传、临床和神经影像学标志物，这对于揭示疾病的发病机制以及患者的进展监测都非常重要。高通量技术和系统生物学方法可以支持识别有效的分子指纹，并建立动态网络生物标志物。重点放在与差异表达的转录物、修饰的蛋白质模体和改变的代谢谱相关的多组学数据集和失调途径上。虽然没有能够终止神经退行性过程的治疗方法，而 L-DOPA 替代疗法是最有效的治疗方法，但许多治疗方案，如多巴胺受体激动剂、MAO-B 抑制剂和胆碱酯酶抑制剂，代表了候选治疗方法，同时为药物重定位提供了有价值的基于网络的方法。用于可视化、聚类和验证分子和临床数据集的计算方法和生物信息学平台为诊断处理和治疗途径提供了重要的见解。
