Are ME and MCS disease mechanisms linked through TRP ion channel dysfunction and ER stress?

Myalgic encephalomyelitis (ME) patients have increased level of WASF3, disrupted mitochondrial respiration, and this is related to Endoplasmic Reticulum (ER) stress (1).

Griffith University suggest ME is a Transient Receptor Potential (TRP) ion channelopathy (2).

TRP channels may be leading actors in ER stress modulation (3).

Many ME patients have Multiple Chemical Sensitivity (MCS). MCS disease mechanism is related to TRPA1 and TRPV1 (4). 

MCS patients do not tolerate environmental irritants, including volatile/semivolatile chemicals, (eg wood smoke and perfume).

Recent findings demonstrated that TRPA1 and TRPV3 channel's activity (using wood smoke particle exposure) is directly correlated to the ER stress process in an opposite manner (5).

This result has been further investigated, and has resulted in a hypothesis for how TRPA1 activation may affect the expression/function of TRPs involved in calcium handling (TRPV1 and TRPV3) and cytotoxic Endoplasmic Reticulum stress, thus modulating responses to TRPA1 stimuli (6):

Figure 12 from reference 6.    Link to figure.

Are ME and MCS disease mechanisms linked through TRP ion channel dysfunction and ER stress?

References

1) Wang PY, Ma J, Kim YC, Son AY, Syed AM, Liu C, Mori MP, Huffstutler RD, Stolinski JL, Talagala SL, Kang JG, Walitt BT, Nath A, Hwang PM. WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2023 Aug 22;120(34):e2302738120. doi: 10.1073/pnas.2302738120. Epub 2023 Aug 14. PMID: 37579159; PMCID: PMC10450651.

https://www.pnas.org/doi/10.1073/pnas.2302738120

2) Du Preez S, Eaton-Fitch N, Smith PK, Marshall-Gradisnik S. Altered TRPM7-Dependent Calcium Influx in Natural Killer Cells of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Biomolecules. 2023 Jun 26;13(7):1039. doi: 10.3390/biom13071039. PMID: 37509075; PMCID: PMC10377690.

https://www.mdpi.com/2218-273X/13/7/1039

3) Vestuto V, Di Sarno V, Musella S, Di Dona G, Moltedo O, Gomez-Monterrey IM, Bertamino A, Ostacolo C, Campiglia P, Ciaglia T. New Frontiers on ER Stress Modulation: Are TRP Channels the Leading Actors? Int J Mol Sci. 2022 Dec 22;24(1):185. doi: 10.3390/ijms24010185. PMID: 36613628; PMCID: PMC9820239.

https://www.mdpi.com/1422-0067/24/1/185

4) Molot J, Sears M, Anisman H. Multiple chemical sensitivity: It's time to catch up to the science. Neurosci Biobehav Rev. 2023 Aug;151:105227. doi: 10.1016/j.neubiorev.2023.105227. Epub 2023 May 10. PMID: 37172924.

https://www.sciencedirect.com/science/article/pii/S0149763423001963

5) Nguyen ND, Memon TA, Burrell KL, Almestica-Roberts M, Rapp E, Sun L, Scott AF, Rower JE, Deering-Rice CE, Reilly CA. Transient Receptor Potential Ankyrin-1 and Vanilloid-3 Differentially Regulate Endoplasmic Reticulum Stress and Cytotoxicity in Human Lung Epithelial Cells After Pneumotoxic Wood Smoke Particle Exposure. Mol Pharmacol. 2020 Nov;98(5):586-597. doi: 10.1124/molpharm.120.000047. Epub 2020 Sep 16. PMID: 32938721; PMCID: PMC7569310.

https://pubmed.ncbi.nlm.nih.gov/32938721/

6) Rapp E, Lu Z, Sun L, Serna SN, Almestica-Roberts M, Burrell KL, Nguyen ND, Deering-Rice CE, Reilly CA. Mechanisms and Consequences of Variable TRPA1 Expression by Airway Epithelial Cells: Effects of TRPV1 Genotype and Environmental Agonists on Cellular Responses to Pollutants in Vitro and Asthma. Environ Health Perspect. 2023 Feb;131(2):27009. doi: 10.1289/EHP11076. Epub 2023 Feb 27. PMID: 36847817; PMCID: PMC9969990.

https://ehp.niehs.nih.gov/doi/10.1289/EHP11076