Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Laboratory of Technologies for Advanced Therapy (LTTA), Technopole of Ferrara, 44121 Ferrara, Italy.
Biomolecules. 2020 Oct 13;10(10):1437. doi: 10.3390/biom10101437.
Innate immune response is one of our primary defenses against pathogens infection, although, if dysregulated, it represents the leading cause of chronic tissue inflammation. This dualism is even more present in the central nervous system, where neuroinflammation is both important for the activation of reparatory mechanisms and, at the same time, leads to the release of detrimental factors that induce neurons loss. Key players in modulating the neuroinflammatory response are mitochondria. Indeed, they are responsible for a variety of cell mechanisms that control tissue homeostasis, such as autophagy, apoptosis, energy production, and also inflammation. Accordingly, it is widely recognized that mitochondria exert a pivotal role in the development of neurodegenerative diseases, such as multiple sclerosis, Parkinson's and Alzheimer's diseases, as well as in acute brain damage, such in ischemic stroke and epileptic seizures. In this review, we will describe the role of mitochondria molecular signaling in regulating neuroinflammation in central nervous system (CNS) diseases, by focusing on pattern recognition receptors (PRRs) signaling, reactive oxygen species (ROS) production, and mitophagy, giving a hint on the possible therapeutic approaches targeting mitochondrial pathways involved in inflammation.
先天免疫反应是我们抵御病原体感染的主要防御机制之一，但如果失调，它将成为慢性组织炎症的主要原因。这种双重性在中枢神经系统中更为明显，其中神经炎症对于激活修复机制非常重要，但同时也会导致释放有害因子，从而诱导神经元丧失。调节神经炎症反应的关键因素是线粒体。实际上，线粒体负责多种控制组织内稳态的细胞机制，如自噬、细胞凋亡、能量产生，以及炎症。因此，人们普遍认为线粒体在多种神经退行性疾病的发展中发挥着关键作用，如多发性硬化症、帕金森病和阿尔茨海默病，以及在急性脑损伤中，如缺血性中风和癫痫发作。在这篇综述中，我们将描述线粒体分子信号在调节中枢神经系统 (CNS) 疾病中的神经炎症中的作用，重点介绍模式识别受体 (PRR) 信号、活性氧 (ROS) 产生和线粒体自噬，并提示针对炎症相关线粒体途径的可能治疗方法。
