Heat Shock Factor 2 Protects against Proteotoxicity by Maintaining Cell-Cell Adhesion, 2020, Joutsen et al

[Hoopoe]

• HSF2 is required to maintain cell-cell adhesion
• HSF2 deficiency leads to downregulation of cadherin superfamily genes
• Impaired cell-cell adhesion sensitizes cells to prolonged proteotoxic stress
• Cadherin-mediated cell-cell adhesion is a survival determinant upon proteotoxicity

https://www.cell.com/cell-reports/fulltext/S2211-1247(19)31694-8

We demonstrate that HSF2-dependent maintenance of cadherin-mediated cell-cell adhesion is required for protection against stress induced by proteasome inhibition. This study identifies HSF2 as a key regulator of cadherin superfamily genes and defines cell-cell adhesion as a determinant of proteotoxic stress resistance.

This suggests that the increased expression of cadherins in ME/CFS might be a response to a specific type of stressor. Has HSF2 been studied in ME/CFS?

 

[Midnattsol]

I can't remember to have seen HSF2, but HSP27 and HSP90 have been looked at previously in "Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins". I wish more studies would go into what could potentially go wrong after exertion, such as this.

 

[Hutan]

I do think that cadherins are worth looking at more.

Toxins from some dinoflagellates disrupt cadherin function. This may be a mode of action in ciguatera fish poisoning (CFP). Some people affected by CFP go on to develop a chronic illness that is a lot like ME/CFS. (I haven't looked into this in detail, but just wanted to note the potential similarity.)

 

[Hoopoe]

Something like heat shock proteins being dysregulated might explain the poor stress and exertion tolerance of patients (they don't just protect cells against heat shock but against many types of stressors).

 

[Midnattsol]

Something like heat shock proteins being dysregulated might explain the poor stress and exertion tolerance of patients (they don't just protect cells against heat shock but against many types of stressors).

Yes There are some more studies from around the same time period as the one I posted above, though if I remember correctly they are all small and criteriria for diagnosis doesn't contain PEM.