Fathi Mobina, Vakili Kimia, Yaghoobpoor Shirin, Qadirifard Mohammad Sadegh, Kosari Mohammadreza, Naghsh Navid, Asgari Taei Afsaneh, Klegeris Andis, Dehghani Mina, Bahrami Ashkan, Taheri Hamed, Mohamadkhani Ashraf, Hajibeygi Ramtin, Rezaei Tavirani Mostafa, Sayehmiri Fatemeh
Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Nursing and Midwifery, Islamic Azad University, Tehran, Iran.
Front Aging Neurosci. 2022 Jul 4;14:855776. doi: 10.3389/fnagi.2022.855776. eCollection 2022.
Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by neuroinflammation, formation of Lewy bodies, and progressive loss of dopaminergic neurons in the substantia nigra of the brain. In this review, we summarize evidence obtained by animal studies demonstrating neuroinflammation as one of the central pathogenetic mechanisms of PD. We also focus on the protein factors that initiate the development of PD and other neurodegenerative diseases. Our targeted literature search identified 40 pre-clinical and studies written in English. Nuclear factor B (NF-kB) pathway is demonstrated as a common mechanism engaged by neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6hydroxydopamine (6-OHDA), as well as the bacterial lipopolysaccharide (LPS). The α-synuclein protein, which plays a prominent role in PD neuropathology, may also contribute to neuroinflammation by activating mast cells. Meanwhile, 6-OHDA models of PD identify microsomal prostaglandin E synthase-1 (mPGES-1) as one of the contributors to neuroinflammatory processes in this model. Immune responses are used by the central nervous system to fight and remove pathogens; however, hyperactivated and prolonged immune responses can lead to a harmful neuroinflammatory state, which is one of the key mechanisms in the pathogenesis of PD.
帕金森病（PD）是第二常见的神经退行性疾病，其特征为神经炎症、路易小体的形成以及大脑黑质中多巴胺能神经元的逐渐丧失。在本综述中，我们总结了动物研究获得的证据，这些证据表明神经炎症是PD的核心致病机制之一。我们还关注引发PD和其他神经退行性疾病发展的蛋白质因子。我们有针对性的文献检索确定了40项临床前研究以及用英文撰写的研究。核因子κB（NF-κB）途径被证明是1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）和6-羟基多巴胺（6-OHDA）等神经毒素以及细菌脂多糖（LPS）所涉及的共同机制。在PD神经病理学中起重要作用的α-突触核蛋白，也可能通过激活肥大细胞促进神经炎症。同时，PD的6-OHDA模型确定微粒体前列腺素E合酶-1（mPGES-1）是该模型中神经炎症过程的促成因素之一。中枢神经系统利用免疫反应来对抗和清除病原体；然而，过度激活和持续的免疫反应会导致有害的神经炎症状态，这是PD发病机制中的关键机制之一。
