Prevention of Atrial Fibrillation: Putting Proteostasis Derailment Back on Track

[www.ncbi.nlm.nih.gov]

I found this interesting. I actually was googling “maple syrup urine disease” and did a cross search to see if there is any connection with afib. I found this hit above. I can’t totally understand the article so I wonder if anyone reading this great article to see if these two are connected.

For those never hearing of MSUD, here is a link:
[www.nhs.uk].

If there is a connection please comment. 1 in 87,000 have MSUD. That said, there are some rare folks who can’t get fixed with ablations. If there is a connection, then that may explain why some rare folks may not be successful in being afib free.

From the abstract:

Quote

Recent discoveries revealed that the derailment of specific molecular proteostasis pathways drive electrical conduction disorders, contractile dysfunction and AF. The degree of this so-called ‘electropathology’ corresponds to the response to anti-AF treatment. Hence, to develop effective therapies to prevent AF, understanding the molecular mechanisms is of key importance. In this review, we highlight the key modulators of proteostasis derailment and describe the mechanisms that explain how they affect electrical and contractile function in atrial cardiomyocytes and AF. The key modulators of proteostasis derailment include (1) exhaustion of cardioprotective heat shock proteins (HSPs), (2) excessive endoplasmic reticulum (ER) stress and downstream autophagic protein degradation, (3) histone deacetylase 6 (HDAC6)-induced microtubule disruption, (4) activation of DNA damage-PARP1 activation and NAD+ axis and (5) mitochondrial dysfunction. Furthermore, we discuss druggable targets within these pathways that are involved in the prevention of proteostasis derailment, as well as the targets that aid in the recovery from AF. Finally, we will elaborate on the most favorable druggable targets for (future) testing in patients with AF, as well as drugs with potential benefits for AF recovery.

Searching on proteostasis, degradation thereof appears to be a hallmark of aging. From your link, MSUD appears to be congenital? At young ages, frank MSUD seems to create very severe issues.

Though your first link looks at druggable targets for afibbers, I do have lifestyle practices to possibly impact some of these targets. I do 30 minutes in a near infrared heat lamp sauna most days I'm at home to stimulate HSPs (I generally sweat a few pounds of water). To upregulate autophagy, I exercise (mostly fasted) and eat in a compressed eating window daily (8 hours or less) with some longer duration fasts (up to 7 days) infrequently. Beta hydroxybutyrate (BH is a known HDAC inhibitor, though I've not been able to find out if it inhibits HDAC6. On a morning fingerstick test, I always test positive for some serum BHB, even after days where I've increased my carb and calorie consumption dramatically the day before. An example, last week I had a couple of days eating ~5000 calories with 400 grams of carbs as other days had been fairly calorically restricted. The serum BHB really increases materially after calorically restricted or frank fasting days. I also target improving mitochondrial function through nutrition as well as Zone 2 and HIIT exercise. I don't have the background or ways to test whether my approaches make any difference.