Review The Role Of Α7 Nicotinic Acetylcholine Receptors In Post-Acute Sequelae Of Covid-19, 2024, Skok

[SNT Gatchaman]

The Role Of Α7 Nicotinic Acetylcholine Receptors In Post-Acute Sequelae Of Covid-19
Skok

Post-Acute Sequelae of COVID-19 or Long COVID becomes evident some weeks to months following acute COVID-19. Symptoms include cognitive impairment and varying degrees of memory loss with no definitive etiologies or efficacious therapies forthcoming even after four years of the SARS-Cov2 pandemic virus.

The aim of this review is to demonstrate the important role of α7 nicotinic acetylcholine receptors in both acute COVID-19 and Long COVID. Evidence presented implicates immune mechanisms stimulated by SARS-Cov-2 S-protein fragment 674685 that possesses homology with α7-specific ligands. Cognitive dysfunctions observed in Long COVID patients may be derived from anti-idiotypic α7-specific antibodies stimulated by (674685)-specific antibodies. Therapeutic interventions capable of neutralizing these antibodies and restoring full functions of α7 nicotinic acetylcholine receptors appear to be of paramount importance in post-acute sequelae of COVID-19.

Link | Paywall (The International Journal of Biochemistry & Cell Biology)

 

[SNT Gatchaman]

The members of nAChR family are ligand-gated ion channels present in neuro-muscular junctions, brain and autonomic ganglia, as well as in many non-excitable cells. The nAChRs composed of α7 subunits were also found in mitochondria and cell nuclei outer membranes. They are involved in regulating cell survival, adhesion and proliferation, as well as neurotransmitter and cytokine release. They can function/signal both ionotropically and metabotropically; however, their ion channel is quickly desensitized. Therefore, most probably, their functions are mainly mediated in ion-independent manner, through conformational/allosteric movements affecting neighboring receptors and signaling molecules.

SARS(674-685) peptide competed with α7-specific antibodies for the binding to α7(179-190) fragment and attenuated cytochrome c release from mitochondria stimulated with Ca2+ similarly to other α7-selective ligands including α7-binding fragment of α-cobratoxin. It was suggested that when the virus penetrates the infected cell and its protein part is cleaved by cellular proteases, SARS(674-685) peptide can influence mitochondria and support the cell viability during the period necessary for virus replication by inhibiting mitochondria apoptosis pathway.

Assuming that α7 nAChRs are the key targets for pathogenic antibodies, the most evident therapeutic solution to overcome their influence is the use of α7-selective agonists, which stimulate α7 nAChR signaling and can prevent α7(179-190)-specific antibody binding (because α7(179-190) fragment contains the elements of agonist binding site). AChE inhibitors can also help by increasing the endogenous acetylcholine levels.

 

[Jonathan Edwards]

Cognitive dysfunctions observed in Long COVID patients may be derived from anti-idiotypic α7-specific antibodies stimulated by (674685)-specific antibodies.

There may be some interesting points raised in this review but invoking anti-idiotypes is almost certainly invalid.

Years ago there was an idea (Jerne's theory) that anti-idiotype antibodies would mimic the original antigen. Basically if the antigen is key and an antibody a lock then an anti-antibody would look like a key again. But just like locks and keys it doesn't work like that because locks and keys are quite different in their shape otherwise. A lock cannot fit into another lock as a key.