Quercetin binding accelerates prion fibrillation into proteinase sensitive and loosely structured amyloids (Yu et al, 2022)

[SNT Gatchaman]

Quercetin binding accelerates prion fibrillation into proteinase sensitive and loosely structured amyloids
Kun-Hua Yu, Cheng-Ping Jheng, Cheng-I Lee

Amyloidoses are caused by the deposition of amyloid fibrils ascribed to protein misfolding. In this study, we examined the antiamyloidogenic and antioxidative activities of quercetin, a plant flavonol from the flavonoid group of polyphenols, on mouse prion protein (moPrP) with biophysical approaches.

As the results show, quercetin binds to the C-terminal region of moPrP, and quercetin binding does not affect the structure of moPrP. However, quercetin binding accelerates moPrP fibrillation and changes the structure of moPrP fibrils. Unlike typical prion fibrils, quercetin-bound fibrils are sensitive to proteinase K and are loosely structured. Moreover, due to high antioxidant activity of flavonoid, quercetin-bound fibrils lack imbalance of free radicals and, therefore, they are nontoxic towards neuroblastoma cells.

The quercetin shows its uniqueness from typical antiamyloidogenic drugs which either suppress the development of amyloid or eliminate formed amyloids. Quercetin binding converts moPrP into protease-sensitive and non-cytotoxic fibrils. This work provides a powerful resolution in the advancement of antiamyloidogenic treatment.

Link | PDF

 

[Husband of]

Could someone please explain what is the relevance of this to MECFS?

 

[SNT Gatchaman]

On the basis that we don't know the cause of ME/CFS, it's reasonable to look at other diseases that we know a little better or that are being researched in parallel for clues. Some of these diseases may share underlying mechanisms. I would be surprised if, when the answer to ME/CFS is finally here, there is zero overlap with things like: pre-eclampsia, migraine, MS, ALS and other neurodegenerative disease, diabetes, aspects of cardiovascular disease and cancer — regardless of what we think their mechanisms are currently.

There is evidence that neuroinflammation and dysfunction of the blood brain barrier may be part of ME & LC. Things like abnormal fibrin deposition may be a secondary and damaging effect. Perhaps this can never lead to neurodegeneration. Perhaps there's a long-term risk of damage with amyloid development in some (although that may be a marker for something upstream).

I think a number of people take or have tried quercetin. This paper suggests it may be protective against a form of long-term neuronal injury. Whether that could help in ME is unknown, but I thought it might be worth recording here in the "other" section where it's searchable in the future.