Gouda Noha A, Elkamhawy Ahmed, Cho Jungsook
College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang 10326, Korea.
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Biomedicines. 2022 Feb 3;10(2):371. doi: 10.3390/biomedicines10020371.
Parkinson's disease (PD) is a neurodegenerative disorder pathologically distinguished by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Muscle rigidity, tremor, and bradykinesia are all clinical motor hallmarks of PD. Several pathways have been implicated in PD etiology, including mitochondrial dysfunction, impaired protein clearance, and neuroinflammation, but how these factors interact remains incompletely understood. Although many breakthroughs in PD therapy have been accomplished, there is currently no cure for PD, only trials to alleviate the related motor symptoms. To reduce or stop the clinical progression and mobility impairment, a disease-modifying approach that can directly target the etiology rather than offering symptomatic alleviation remains a major unmet clinical need in the management of PD. In this review, we briefly introduce current treatments and pathophysiology of PD. In addition, we address the novel innovative therapeutic targets for PD therapy, including α-synuclein, autophagy, neurodegeneration, neuroinflammation, and others. Several immunomodulatory approaches and stem cell research currently in clinical trials with PD patients are also discussed. Moreover, preclinical studies and clinical trials evaluating the efficacy of novel and repurposed therapeutic agents and their pragmatic applications with encouraging outcomes are summarized. Finally, molecular biomarkers under active investigation are presented as potentially valuable tools for early PD diagnosis.
帕金森病(PD)是一种神经退行性疾病,其病理特征是黑质致密部多巴胺能神经元变性。肌肉僵硬、震颤和运动迟缓都是PD的临床运动特征。PD的病因涉及多种途径,包括线粒体功能障碍、蛋白质清除受损和神经炎症,但这些因素如何相互作用仍未完全清楚。尽管PD治疗已取得许多突破,但目前尚无治愈方法,只有缓解相关运动症状的试验。为了减少或阻止临床进展和运动功能障碍,一种能够直接针对病因而非仅缓解症状的疾病修饰方法仍然是PD治疗中尚未满足的主要临床需求。在本综述中,我们简要介绍了PD的当前治疗方法和病理生理学。此外,我们还探讨了PD治疗的新型创新治疗靶点,包括α-突触核蛋白、自噬、神经退行性变、神经炎症等。还讨论了目前在PD患者中进行临床试验的几种免疫调节方法和干细胞研究。此外,总结了评估新型和重新利用治疗药物疗效及其具有令人鼓舞结果的实际应用的临床前研究和临床试验。最后,介绍了正在积极研究的分子生物标志物,它们可能是早期PD诊断的有价值工具。