Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Nile University of Nigeria, Abuja, Nigeria.
Technical University of Sofia, Klement Ohridksi 8, Sofia 1000, Bulgaria.
Pharmacol Res. 2021 May;167:105557. doi: 10.1016/j.phrs.2021.105557. Epub 2021 Mar 15.
Evidence indicates a critical role of neuroinflammatory response as an underlying pathophysiological process in several central nervous system disorders, including neurodegenerative diseases. However, the molecular mechanisms that trigger neuroinflammatory processes are not fully known. The discovery of bitter taste receptors in regions other than the oral cavity substantially increased research interests on their functional roles in extra-oral tissues. It is now widely accepted that bitter taste receptors, for instance, in the respiratory, intestinal, reproductive and urinary tracts, are crucial not only for sensing poisonous substances, but also, act as immune sentinels, mobilizing defense mechanisms against pathogenic aggression. The relatively recent discovery of bitter taste receptors in the brain has intensified research investigation on the functional implication of cerebral bitter taste receptor expression. Very recent data suggest that responses of bitter taste receptors to neurotoxins and microbial molecules, under normal condition, are necessary to prevent neuroinflammatory reactions. Furthermore, emerging data have revealed that downregulation of key components of the taste receptor signaling cascade leads to increased oxidative stress and inflammasome signaling in neurons that ultimately culminate in neuroinflammation. Nevertheless, the mechanisms that link taste receptor mediated surveillance of the extracellular milieu to neuroinflammatory responses are not completely understood. This review integrates new data on the molecular mechanisms that link bitter taste receptor sensing to neuroinflammatory responses. The role of bitter taste receptor-mediated sensing of toxigenic substances in brain disorders is also discussed. The therapeutic significance of targeting these receptors for potential treatment of neurodegenerative diseases is also highlighted.
证据表明，神经炎症反应在包括神经退行性疾病在内的几种中枢神经系统疾病中起着关键的病理生理作用。然而，触发神经炎症过程的分子机制尚不完全清楚。苦味受体在口腔以外的区域被发现，这大大增加了人们对其在口腔外组织中的功能作用的研究兴趣。现在人们普遍认为，苦味受体（例如，在呼吸道、肠道、生殖和泌尿系统中）不仅对感知有毒物质至关重要，而且还作为免疫哨兵，动员防御机制抵御致病侵袭。最近在大脑中发现苦味受体，这促使人们对大脑中苦味受体表达的功能意义进行了更多的研究调查。最近的数据表明，在正常情况下，苦味受体对神经毒素和微生物分子的反应对于防止神经炎症反应是必要的。此外，新出现的数据表明，味觉受体信号级联中的关键成分下调会导致神经元中的氧化应激和炎症小体信号增加，最终导致神经炎症。然而，将味觉受体介导的细胞外环境监测与神经炎症反应联系起来的机制尚不完全清楚。这篇综述整合了将苦味受体感知与神经炎症反应联系起来的分子机制的新数据。还讨论了苦味受体介导的对脑内毒素物质的感知在脑疾病中的作用。还强调了针对这些受体作为治疗神经退行性疾病的潜在治疗方法的治疗意义。
