Department of Zoology, School of Biological Sciences, Central University of Punjab, Ghudda, Bathinda, Punjab 151401, India.
Department of Zoology, School of Biological Sciences, Central University of Punjab, Ghudda, Bathinda, Punjab 151401, India.
Ageing Res Rev. 2022 Sep;80:101681. doi: 10.1016/j.arr.2022.101681. Epub 2022 Jul 4.
Parkinson's disease (PD) is the second-most-common neurodegenerative disease characterized by motor and non-motor dysfunctions, which currently affects about 10 million people worldwide. Gradual death and progressive loss of dopaminergic neurons in the pars compacta region of substantia nigra result in striatal dopamine deficiency in PD. Specific mutation with further aggregation of α-synuclein in the intraneuronal inclusion bodies is considered the neuropathological hallmark of this disease. PD is often associated with various organelle dysfunctions inside a dopaminergic neuron, including mitochondrial damage, proteasomal impairment, and production of reactive oxygen species, thus causing subsequent neuronal death. Apart from several genetic and non-genetic risk factors, emerging research establishes an association between cardiovascular diseases, including coronary heart disease, myocardial infarction, congestive heart failure, and ischemic stroke with PD. The majority of these cardiovascular diseases have an origin from atherosclerosis, where endothelial dysfunction following thrombus formation is significantly regulated by blood platelet. This non-nucleated cell fragment expresses not only neuron-specific molecules and receptors but also several PD-specific biomarkers such as α-synuclein, parkin, PTEN-induced kinase-1, tyrosine hydroxylase, dopamine transporter, thus making platelet a suitable peripheral model for PD. Besides its similarity with a dopaminergic neuron, platelet structural alterations, as well as functional abnormalities, are also evident in PD. However, the molecular mechanism behind platelet dysfunction is still elusive and quite controversial. This state-of-the-art review describes the detailed mechanism of platelet impairment in PD, addressing the novel platelet-associated therapeutic drug candidates for plausible PD management.
帕金森病（PD）是第二大常见的神经退行性疾病，其特征为运动和非运动功能障碍，目前全球约有 1000 万人受其影响。黑质致密部多巴胺能神经元逐渐死亡和进行性丧失导致 PD 患者纹状体多巴胺缺乏。特定突变进一步导致α-突触核蛋白在神经元内包涵体中的聚集被认为是这种疾病的神经病理学标志。PD 常伴有多巴胺能神经元内各种细胞器功能障碍，包括线粒体损伤、蛋白酶体功能障碍和活性氧的产生，从而导致随后的神经元死亡。除了几个遗传和非遗传风险因素外，新兴研究还确定了心血管疾病（包括冠心病、心肌梗死、充血性心力衰竭和缺血性中风）与 PD 之间的关联。这些心血管疾病大多数起源于动脉粥样硬化，血栓形成后内皮功能障碍受到血小板的显著调节。这个无核细胞片段不仅表达神经元特异性分子和受体，还表达几种 PD 特异性生物标志物，如α-突触核蛋白、parkin、PTEN 诱导的激酶-1、酪氨酸羟化酶、多巴胺转运体，因此血小板是 PD 的合适外周模型。除了与多巴胺能神经元的相似性外，血小板的结构改变和功能异常在 PD 中也很明显。然而，血小板功能障碍的分子机制仍不清楚，且颇具争议。这篇综述详细描述了血小板在 PD 中的损伤机制，并探讨了新型血小板相关治疗药物候选物用于 PD 管理的可能性。
