Hi all ,Going through some MND research on the Australian site....

Hi all ,

Going through some MND research on the Australian site. I noticed an article , I have quoted the text by GINA MANTICA | Boston Children's Hospital March 13, 2023.

"To better understand the relationship between gasdermin E and neurodegeneration, the team created models of ALS motor neurons by transforming stem cells from people with ALS into neurons. The researchers found that gasdermin E is present at high levels in these neurons. When the researchers silenced gasdermin E in these neurons, the axons and mitochondria of these cells were shielded from damage.The team then wanted to test whether the effects they saw in cells could translate to improvements in symptoms related to neurodegeneration. The researchers silenced gasdermin E in a mouse model of ALS and found that this delayed the progression of symptoms and led to protected motor neurons, longer axons, and less overall inflammation. These findings suggest that gasdermin E drives changes to neurons that may contribute to disease progression".

My thoughts next paragraph.

So what does that mean for Monepantel. Gasdermin a signalling translator or conductor in the body. Everything is multifaceted in our immune DNA system with checkpoints everywhere. Monepantel as an mTOR inhibitor , inhibits Gasdermin by suppressing 2 out of the 3 signalling pathways thus inhibiting the inflammatory pathway and increasing autophagy or clearing the misfolded proteins in the brain. It does this by inhibition of Rip1 and Rip3.

Yet another example of detrimental RIPK3-dependent signaling is the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Loss of the protein optineurin (Optn), which has been implicated in ALS, sensitizes glial cells of the CNS to necroptosis, leading to demyelination and axonal degeneration (85). This is clearly demonstrated in mouse embryonic fibroblasts (MEFs) derived from Optn−/− mice, as well as in the spinal cords of Optn−/− mice, which have increased levels of complex-associated RIPK1, RIPK3, and phospho-MLKL, which can be used as a marker of necroptosis. Interestingly, the axonal pathology and hindlimb weakness of Optn-deficient mice was rescued in Optn−/−Ripk1D138N/D138N mice, as well as Optn−/−Ripk3−/− double mutant mice, and treatment of Optn−/− mice with Nec-1s (a highly specific inhibitor of RIPK1 catalytic activity) led to a reduction of neuropathology (85). Together, these data suggest that uncontrolled RIPK3-dependent necroptosis can be harmful in the context of ALS, and have led to efforts to target this pathway pharmacologically .

RIPK3 in cell death and inflammation: The Good, the Bad, and the UglySusana Orozco and Andrew Oberst2017.


Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsisJoseph K Rathkey et al. Sci Immunol. 2018.

Yes , I know it's technical, just keeping you in the loop on why this drug is working.

Cheers

Kpax