HYPOTHESIS/PROPOSAL: MODIFICATION of EXISTING STUDY: EPIGENETIC CLOCKS as TRACKING MECHANISMS FOR INJURY and DISEASE--WITH or W/OUT INTEGRATION for FINDING CELLULAR and EPIGENTIC AGE and DAMAGE
HYPOTHESIS/PROPOSAL: MODIFICATION of EXISTING STUDY: EPIGENETIC CLOCKS as TRACKING MECHANISMS FOR INJURY and DISEASE--WITH or W/OUT INTEGRATION for FINDING CELLULAR and EPIGENTIC AGE and DAMAGE
Contribution of the cGAS-STING to the progressive degeneration of amyotrophic lateral sclerosis (ALS) / Lou Gehrig's disease
cGAS and DDX41-STING mediated intrinsic immunity spreads intercellularly to promote neuroinflammation in SOD1 ALS model (2022)
SUMMARY
Neuroinflammation exacerbates the progression of SOD1-driven amyotrophic lateral sclerosis (ALS), although the underlying mechanisms remain largely unknown. Herein, we demonstrate that misfolded SOD1 (SOD1Mut)-causing ALS results in mitochondrial damage, thus triggering the release of mtDNA and an RNA:DNA hybrid into the cytosol in an mPTP-independent manner to activate IRF3- and IFNAR-dependent type I interferon (IFN-I) and interferon-stimulating genes. The neuronal hyper-IFN-I and pro-inflammatory responses triggered in ALS-SOD1Mut were sufficiently robust to cause a strong physiological outcome in vitro and in vivo. cGAS/DDX41-STING-signaling is amplified in bystander cells through inter-neuronal gap junctions. Our results highlight the importance of a common DNA-sensing pathway between SOD1 and TDP-43 in influencing the progression of ALS.
When you mentioned CpG islands G4Ps sprung to mind, as these are also associated with C & G, as well as mRNA m1u gene therapies:
DNA G-quadruplex stability, position and chromatin accessibility are associated with CpG island methylation (2020)
"... Using methylation data from human embryonic stem cells (hESCs) and three hESC-derived populations, we showed that hypomethylated CpGs located inside CGI (CGI/CpG) tend to be associated with highly stable G4FS (Minimum free energy ≤ -30 kcal·mol-1 )."
I am about to update this stack and add the rest of it I was about to place in a paper--still needs more work with the other injury mechanism.
Here's a hint: the clots people are seeing? they are not clots. They are something else. When you see it, you cannot unsee it.
Also interesting, that men in a certain age bracket get myocarditis at a specific ratio. That one is also simple to explain. Then you think, why was that not explained by cardiologists
Contribution of the cGAS-STING to the progressive degeneration of amyotrophic lateral sclerosis (ALS) / Lou Gehrig's disease
cGAS and DDX41-STING mediated intrinsic immunity spreads intercellularly to promote neuroinflammation in SOD1 ALS model (2022)
SUMMARY
Neuroinflammation exacerbates the progression of SOD1-driven amyotrophic lateral sclerosis (ALS), although the underlying mechanisms remain largely unknown. Herein, we demonstrate that misfolded SOD1 (SOD1Mut)-causing ALS results in mitochondrial damage, thus triggering the release of mtDNA and an RNA:DNA hybrid into the cytosol in an mPTP-independent manner to activate IRF3- and IFNAR-dependent type I interferon (IFN-I) and interferon-stimulating genes. The neuronal hyper-IFN-I and pro-inflammatory responses triggered in ALS-SOD1Mut were sufficiently robust to cause a strong physiological outcome in vitro and in vivo. cGAS/DDX41-STING-signaling is amplified in bystander cells through inter-neuronal gap junctions. Our results highlight the importance of a common DNA-sensing pathway between SOD1 and TDP-43 in influencing the progression of ALS.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9194172/
Thanks Christie.
When you mentioned CpG islands G4Ps sprung to mind, as these are also associated with C & G, as well as mRNA m1u gene therapies:
DNA G-quadruplex stability, position and chromatin accessibility are associated with CpG island methylation (2020)
"... Using methylation data from human embryonic stem cells (hESCs) and three hESC-derived populations, we showed that hypomethylated CpGs located inside CGI (CGI/CpG) tend to be associated with highly stable G4FS (Minimum free energy ≤ -30 kcal·mol-1 )."
https://pubmed.ncbi.nlm.nih.gov/31532882/
I am about to update this stack and add the rest of it I was about to place in a paper--still needs more work with the other injury mechanism.
Here's a hint: the clots people are seeing? they are not clots. They are something else. When you see it, you cannot unsee it.
Also interesting, that men in a certain age bracket get myocarditis at a specific ratio. That one is also simple to explain. Then you think, why was that not explained by cardiologists
I have seen the list of the makeup of them. Not my first rodeo.
Same system causing miscarriages.
Boom!