Fiebich Bernd L, Batista Carla Ribeiro Alvares, Saliba Soraya Wilke, Yousif Nizar M, de Oliveira Antonio Carlos Pinheiro
Neuroimmunology and Neurochemistry Research Group, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Front Cell Neurosci. 2018 Oct 2;12:329. doi: 10.3389/fncel.2018.00329. eCollection 2018.
Toll-like receptors (TLRs) are a group of receptors widely distributed in the organism. In the central nervous system, they are expressed in neurons, astrocytes and microglia. Although their involvement in immunity is notorious, different articles have demonstrated their roles in physiological and pathological conditions, including neurodegeneration. There is increasing evidence of an involvement of TLRs, especially TLR2, 4 and 9 in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). In this sense, their expression in microglia might modulate the activity of these cells, which in turn, lead to protective or deleterious effects over neurons and other cells. Therefore, TLRs might mediate the link between inflammation and neurodegenerative diseases. However, further studies have to be performed to elucidate the role of the other TLRs in these diseases and to further prove and confirm the pathophysiological role of all TLRs in neurodegeneration. In this article, we revise and summarize the current knowledge regarding the role of TLRs in neurodegeneration with the focus on the possible functions of these receptors in microglia.
Toll样受体(TLRs)是一类广泛分布于机体的受体。在中枢神经系统中,它们在神经元、星形胶质细胞和小胶质细胞中表达。尽管它们在免疫方面的作用广为人知,但不同的文章已证明它们在包括神经退行性变在内的生理和病理状况中发挥作用。越来越多的证据表明,TLRs,尤其是TLR2、TLR4和TLR9参与了诸如阿尔茨海默病(AD)、帕金森病(PD)和肌萎缩侧索硬化症(ALS)等神经退行性疾病。从这个意义上说,它们在小胶质细胞中的表达可能会调节这些细胞的活性,进而对神经元和其他细胞产生保护或有害作用。因此,TLRs可能介导炎症与神经退行性疾病之间的联系。然而,还需要进行进一步的研究来阐明其他TLRs在这些疾病中的作用,并进一步证明和确认所有TLRs在神经退行性变中的病理生理作用。在本文中,我们回顾并总结了目前关于TLRs在神经退行性变中作用的知识,重点关注这些受体在小胶质细胞中的可能功能。