NEWS: GPCR, Long Covid and Gq/11

News related to COVID and Gq/11
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NEWS: GPCR, Long Covid and Gq/11

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G-Protein-Coupled Receptors, Long Covid and Gq/11

COVID-19

Wallukat G, Hohberger B, Wenzel K, Fürst J, Schulze-Rothe S, Wallukat A, Hönicke AS, Müller J - "Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms" J Transl Autoimmun 4:100100 (2021)
https://www.ncbi.nlm.nih.gov/labs/pmc/a ... MC8049853/
"Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies (fAABs) targeting G-protein coupled receptors (GPCR-fAABs) has been discussed to be involved."

"Investigated patients had between 2 and 7 different GPCR-fAAB (Table 1). This was a surprising unexpected effect. In healthy controls, which are included in many studies, these autoantibodies are only found in a small percentage [37,38]”.

"The astonishing finding of this investigation is the fact that an unusually high number of GPCR-fAABs were detected in the serum of recovered COVID-19 patients who mostly suffered from a variety of different post-COVID-19 symptoms. Due to the functionality of such GPCR-fAABs, the question of whether these GPCR-fAABs may play a role in the development of post-COVID-19 symptoms is raised."

"Two of the identified GPCR-fAABs, observed in over 90% of the investigated COVID-19 patient sera (29/31), were directed against receptors of RAS, namely the angiotensin II AT1 receptor and the angiotensin (1–7) MAS receptor."
SEE also:
  • Canals M, Jenkins L, Kellett E, Milligan G - "Up-regulation of the angiotensin II type 1 receptor by the MAS proto-oncogene is due to constitutive activation of Gq/G11 by MAS" J Biol Chem 281(24):16757-67 (2006)
    https://pubmed.ncbi.nlm.nih.gov/16611642/

    Cabana J, Holleran B, Leduc R, Escher E, Guillemette G, Lavigne P - "Identification of Distinct Conformations of the Angiotensin-II Type 1 Receptor Associated with the Gq/11 Protein Pathway and the β-Arrestin Pathway Using Molecular Dynamics Simulations" J Biol Chem 290(25):15835-15854 (2015)
    https://www.ncbi.nlm.nih.gov/labs/pmc/a ... MC4505491/

    Turu G, Várnai P, Gyombolai P, Szidonya L, Offertaler L, Bagdy G, Kunos G, Hunyady L - "Paracrine transactivation of the CB1 cannabinoid receptor by AT1 angiotensin and other Gq/11 protein-coupled receptors" J Biol Chem 284(25):16914-16921 (2009)
    https://www.ncbi.nlm.nih.gov/labs/pmc/a ... MC2719328/
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What Makes Antibodies Against G Protein-Coupled Receptors so Special? A Novel Concept to Understand Chronic Diseases.

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Riemekasten G, Petersen F, Heidecke H - "What Makes Antibodies Against G Protein-Coupled Receptors so Special? A Novel Concept to Understand Chronic Diseases." Front Immunol 11:564526 (2020) doi: 10.3389/fimmu.2020.564526
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770155/

Expressions of G protein-coupled receptors (GPCR) on immune and tissue resident cells are the consequence of the cellular environment, which is highly variable. As discussed here, antibodies directed to GPCR (GPCR abs), their levels and correlations to other abs, serve as biomarkers for various diseases. They also could reflect the individual interplay between the environment and the immune system. Thus, GPCR abs could display pathogenic chronic conditions and could help to identify disease-related pathways. Moreover, by acting as ligands to their corresponding receptors, GPCR abs modulate autoimmune as well as non-autoimmune diseases. This article introduces GPCR abs as drivers for diseases by their capability to induce a specific signaling and by determining immune cell homeostasis. The identification of the individual GPCR ab function is challenging but might be pivotal in the comprehension of the aetiology of diseases. This, hopefully, will lead to the identification of novel therapeutic strategies. This article provides an overview about concepts and recent developments in research. Accordingly, GPCR abs could represent ideal candidates for precision medicine. Here, we introduce the term antibodiom to cover the network of abs with GPCR abs as prominent players.

"Nevertheless, higher GPCR abs compared to healthy individuals are common in human pathophysiology and were also found in endocrinological diseases (Graves’ Disease or Hashimoto thyroiditis), in gynaecology (preeclampsia), cardiac diseases (heart transplantation, cardiomyopathy, chronic heart failure, orthostatic hypotension, and postural tachycardia syndrome), or in neurologic diseases such as in dementia, Alzheimer Disease, chronic fatigue syndrome (myalgic encephalomyelitis), or in complex regional pain syndromes (6, 13, 20–23)."
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