Kristen Sparrow • October 03, 2021
The α7nAcetylcholine receptor comes up again and again in research on inflammation and has been studied in the context of acupuncture too. Vagal activity is key to natural feedbacks for anti-inflammation. I’ve been monitoring Heart Rate Variability (HRV) for many years which is a measure of autonomic balance. Autonomic balance refers to the relative contributions of the sympathetic nervous system and parasympathetic nervous system (vagus). This talk is from abstracts from the Fourth bioelectric medicine summit. This was the keynote address. The original article can be found here.
The abstract from this presentation is adapted from the following publication: Rothbard JB, Kurnellas MP, Ousman SS, Brownell S, Rothbard JJ, Steinman L. Small Heat Shock Proteins, Amyloid Fibrils, and Nicotine Stimulate a Common Immune Suppressive Pathway with Implications for Future Therapies. Cold Spring Harb Perspect Med. 2019 Jul 1;9(7):a034223. doi: 10.1101/cshperspect.a034223. PMID: 30249602; PMCID: PMC6601455.
The α7 nicotinic acetylcholine receptor (α7nAChR) is central to the anti-inflammatory function of the vagus nerve in a physiological mechanism termed the inflammatory reflex. Studies on the inflammatory reflex have been instrumental for the current development of the field of bioelectronic medicine. An independent investigation of the biological role of αB-crystallin (HspB5), the most abundant gene transcript present in active multiple sclerosis lesions in human brains, also led to α7nAChR. Induction of experimental autoimmune encephalomyelitis (EAE) in HspB5−/− mice results in greater paralytic signs, increased levels of proinflammatory cytokines, and T-lymphocyte activation relative to wild-type animals. Administration of HspB5 was therapeutic in animal models of multiple sclerosis, retinal and cardiac ischemia, and stroke. Structure–activity studies established that residues 73–92 were as potent as the parent protein, but only when it formed amyloid fibrils. Amyloid fibrils and small heat shock proteins (sHsps) selectively bound α7nAChR on peritoneal macrophages (MΦs) and B lymphocytes, converting the MΦs to an immune suppressive phenotype and mobilizing the migration of both cell types from the peritoneum to secondary lymph organs. Finally, our approach in translation to the clinic is for the development of small molecules that are orally active to modulate the α7nAChR.