Therapeutic Potential of α7 Nicotinic Acetylcholine Receptor Agonists in a Murine Model of Rheumatoid Arthritis

Therapeutic Potential of α7 Nicotinic Acetylcholine Receptor Agonists in a Murine Model of Rheumatoid Arthritis

According to van Maanen et al., and their recent publication in PLoS One, two new experimental compounds affecting the acetylcholine-receptor system are able to delay collagen-induced arthritis (CIA) in mice, showing the therapeutic potential of chemicals targeting the α7 subunit of nicotinic acetylcholine receptors (α7nAChR).

Previous research revealed that the efferent vagus nerve may decrease peripheral inflammation via inhibition of the release of inflammatory cytokines. This effect is dependent on the activation of nicotinic acetylcholine receptors (nACh), mainly the α7 subunit, expressed on macrophages that respond to acetylcholine (ACh), the main cholinergic neurotransmitter released by the efferent vagus nerve.

The vagus/cholinergic anti-inflammatory effect was documented in animal disease models such as carrageenan-induced inflammation and collagen-induced arthritis (L. Borovikova et al., 2000; Y. Levine et al., 2014), where the intraperitoneal administration of α7 nAChR agonists was also proven to be effective (M. van Maanen et al., 2009). Thus, the identification and use of specific α7 agonists that are able to inhibit inflammation stimulated the development of selective compounds aimed to the modulation of α7 nAChR.

In the PLoS ONE study, Marjolein van Maanen et al., used two novel α7nAChR selective agonists, PMP-311 and PMP-072, studied their effects and tested their therapeutic potential in the collagen-induced arthritis model in mice. In this study, the authors found that these compounds were effective in reducing arthritis incidence, preventing onset of disease, and protecting against synovial inflammation and joint destruction. The report also showed that α7nAChR agonists may exert anti-inflammatory effects independently of ion channel activation.

This study extends previous work showing that α7nAChR ligands may reduce disease activity in animal models of rheumatoid arthritis. This research may also suggest and stimulate the development of new therapeutic strategies or targets in patients with rheumatoid arthritis.

Source: PLoS One, 2015, 10(1):e0116227. DOI:10.1371/journal.pone.0116227
Read More: PLoS One




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