Abstract
This review addresses the role that substance P (SP) and its preferred receptor neurokinin-1 (NK1R) play in neuroinflammation associated with select bacterial, viral, parasitic, and neurodegenerative diseases of the central nervous system. The SP/NK1R complex is a key player in the interaction between the immune and nervous systems. A common effect of this interaction is inflammation. For this reason and because of the predominance in the human brain of the NK1R, its antagonists are attractive potential therapeutic agents. Preventing the deleterious effects of SP through the use of NK1R antagonists has been shown to be a promising therapeutic strategy, as these antagonists are selective, potent, and safe. Here we evaluate their utility in the treatment of different neuroinfectious and neuroinflammatory diseases, as a novel approach to clinical management of CNS inflammation.
Highlights
The substance P (SP)/NK1R system plays an important role in neuroinflammation
Studies involving bacterial infections have shown that SP can synergistically augment Borrelia burgdorferi induced expression of COX-2 in murine microglia[21], and that endogenous SP/NK1R interactions are required for maximal inflammatory responses to in vivo challenge with bacteria such as Neisseria meningitidis or B. burgdorferi[22,23]
Results showed that pharmacological targeting of the NK1R prevented the development of damaging inflammation when administered prophylactically, and limited neuroinflammation associated with S. pneumonia infection
Summary
The SP/NK1R system plays an important role in neuroinflammation. SP is encoded by the TAC1 gene and belongs to a large family of structurally related peptides, the tachykinins. We reviewed preclinical and clinical studies on the effectiveness of NK1R antagonist treatment of CNS inflammation due to bacterial, viral, parasitic or neurodegenerative diseases. Studies involving bacterial infections have shown that SP can synergistically augment Borrelia burgdorferi induced expression of COX-2 in murine microglia[21], and that endogenous SP/NK1R interactions are required for maximal inflammatory responses to in vivo challenge with bacteria such as Neisseria meningitidis or B.
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