Department of Pharmaceutical Sciences, School of Pharmacy and Department of Chemical Engineering, College of Engineering, Northeastern University, Boston, MA, United States of America.
Center for Translational NeuroImaging, Northeastern University, Boston, MA, United States of America.
Biomed Pharmacother. 2022 May;149:112812. doi: 10.1016/j.biopha.2022.112812. Epub 2022 Mar 12.
The clinical translation of therapeutic approaches to combat debilitating neurodegenerative conditions, such as Parkinson's disease (PD), remains as an urgent unmet challenge. The strong molecular association between the pathogenesis of traumatic brain injury (TBI) and the development of parkinsonism in humans has been well established. Therefore, a lot of ongoing research aims to investigate this pathology overlap in-depth, to exploit the common targets of TBI and PD for development of more effective and long-term treatment strategies. This review article intends to provide a detailed background on TBI pathophysiology and its established overlap with PD with an additional emphasis on the recent findings about their effect on perivascular clearance. Although, the traditional animal models of TBI and PD are still being considered, there is a huge focus on the development of combinatory hybrid animal models coupling concussion with the pre-established PD models for a better recapitulation of the human context of PD pathogenesis. Lastly, the therapeutic targets for TBI and PD, and the contemporary research involving exosomes, DNA vaccines, miRNA, gene therapy and gene editing for the development of potential candidates are discussed, along with the recent development of lesser invasive and promising central nervous system (CNS) drug delivery strategies.
治疗方法向治疗使人衰弱的神经退行性疾病（如帕金森病）的临床转化仍然是一个紧迫的未满足的挑战。创伤性脑损伤（TBI）发病机制与人类帕金森病发展之间的强烈分子关联已得到充分证实。因此，许多正在进行的研究旨在深入研究这种病理学重叠，利用 TBI 和 PD 的共同靶点开发更有效和长期的治疗策略。本文旨在提供关于 TBI 病理生理学及其与 PD 建立重叠的详细背景，特别强调最近关于它们对血管周围清除作用的发现。尽管 TBI 和 PD 的传统动物模型仍在考虑之中，但人们非常关注开发组合杂交动物模型，将脑震荡与预先建立的 PD 模型结合起来，以更好地再现 PD 发病机制的人类背景。最后，讨论了 TBI 和 PD 的治疗靶点，以及涉及外泌体、DNA 疫苗、miRNA、基因治疗和基因编辑的当代研究，以开发潜在的候选药物，以及最近开发的较小侵入性和有前途的中枢神经系统（CNS）药物输送策略。
