5 ms·

I searched for Reelin protein and found related articles where rats benefited as well. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166788/ https://www.ncbi.n

I searched for Reelin protein and found related articles where rats benefited as well. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166788/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166788/ https://www.frontiersin.org/articles/10.3389/fncel.2020.00285/full https://www.frontiersin.org/articles/10.3389/fncel.2020.0028... Is Reelin commercially available?

FollowingTheDao 3y ago
It might be low Reelin that protects them. That is the function of must genetic mutations, to slow down the enzyme. So taking Reelin might make you worse. Zinc might increase reelin activity though. https://pubmed.ncbi.nlm.nih.gov/10192793/ https://pubmed.ncbi.nlm.nih.gov/10192793/ It might be that high reelin is protecting but I cannot tell from this study yet what the mutation does. ADDING: Found it. It is a GAIN OF FUNCTION mutation, which means more Reelin will help curb Alzheimer's. And to me that means more zinc will help as well. https://www.nature.com/articles/s41591-023-02318-3 https://www.nature.com/articles/s41591-023-02318-3 RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.
- robwwilliams 3y ago
  These molecular systems are deeply complex and will depend on cascades of interactions. Hang tight. The only generic neuroprotective supplement I can recommend is niacinamide (vitamin B3, non-flushing). See: https://pubmed.ncbi.nlm.nih.gov/28209901/ https://pubmed.ncbi.nlm.nih.gov/28209901/ (yes, in mice! but now in clinical trials for glaucoma and looking good. And yes, glaucoma is not AD, but many/most forms of neurodegenerations are associated with high mitochondrial stress/dysfunction).
  - carlmr 3y ago
    I was wondering what non-flushing meant, and I found this, apparently the non -flushing vitamin B3 is just barely absorbed: http://www.dpic.org/article/professional/niacin-facts-flushing#:~:text=Q%3A%20What%20about%20%22no%2D,does%20not%20produce%20any%20flushing http://www.dpic.org/article/professional/niacin-facts-flushi....
  - FollowingTheDao 3y ago
    wow, you really like dismissing pretty obvious evidence that zinc plays a role in Alzheimer's. It is not complex, it is simple. I believe it is a metabolic disease caused by metabolic disease and genetic risk. That will be unique for everyone, but for most people I feel the answer will be poor zinc handling. And Niacin is all you can come up with? Did you know we make niacin if we have enough B6 and B2?
psb 3y ago
Feels like a "lot" of things help rats for whatever reason though
robwwilliams 3y ago
No, not in any way useful in therapeutics yet. It is a large gene and protein. Delivery to the right cells and neurons in adult humans is well beyond state-of-the-art. But we may be able to mimic its effects with small molecules. https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Term=5649 https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Term=564...

FollowingTheDao 3y ago

It might be low Reelin that protects them. That is the function of must genetic mutations, to slow down the enzyme. So taking Reelin might make you worse. Zinc might increase reelin activity though. https://pubmed.ncbi.nlm.nih.gov/10192793/ https://pubmed.ncbi.nlm.nih.gov/10192793/ It might be that high reelin is protecting but I cannot tell from this study yet what the mutation does. ADDING: Found it. It is a GAIN OF FUNCTION mutation, which means more Reelin will help curb Alzheimer's. And to me that means more zinc will help as well. https://www.nature.com/articles/s41591-023-02318-3 https://www.nature.com/articles/s41591-023-02318-3 RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.

robwwilliams 3y ago
These molecular systems are deeply complex and will depend on cascades of interactions. Hang tight. The only generic neuroprotective supplement I can recommend is niacinamide (vitamin B3, non-flushing). See: https://pubmed.ncbi.nlm.nih.gov/28209901/ https://pubmed.ncbi.nlm.nih.gov/28209901/ (yes, in mice! but now in clinical trials for glaucoma and looking good. And yes, glaucoma is not AD, but many/most forms of neurodegenerations are associated with high mitochondrial stress/dysfunction).
- carlmr 3y ago
  I was wondering what non-flushing meant, and I found this, apparently the non -flushing vitamin B3 is just barely absorbed: http://www.dpic.org/article/professional/niacin-facts-flushing#:~:text=Q%3A%20What%20about%20%22no%2D,does%20not%20produce%20any%20flushing http://www.dpic.org/article/professional/niacin-facts-flushi....
- FollowingTheDao 3y ago
  wow, you really like dismissing pretty obvious evidence that zinc plays a role in Alzheimer's. It is not complex, it is simple. I believe it is a metabolic disease caused by metabolic disease and genetic risk. That will be unique for everyone, but for most people I feel the answer will be poor zinc handling. And Niacin is all you can come up with? Did you know we make niacin if we have enough B6 and B2?

psb 3y ago

Feels like a "lot" of things help rats for whatever reason though

robwwilliams 3y ago

No, not in any way useful in therapeutics yet. It is a large gene and protein. Delivery to the right cells and neurons in adult humans is well beyond state-of-the-art. But we may be able to mimic its effects with small molecules. https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Term=5649 https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Term=564...