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Monday, July 10, 2023 2:27:16 AM
Maybe you can show us a more recent reputable article that confirms neurogenesis does take place in the adult human brain?
If a Rudolph Tanzi paper is all one’s got it’s not great. But I guess some here now likes his contribution to this more recent paper suggesting silencing the SIGMAR1 gene or blocking the Sigma-1 receptor using a S1R antagonist is a way to treat AD.
“Next, the MGH team wanted to learn what happens when MAM levels and activity were intentionally altered. They showed for the first time that preventing assembly of MAMs, either with gene therapy or a drug that blocked a key protein called the sigma-1 receptor (S1R), dramatically decreased beta secretase cleavage of palAPP in axons and lowered Abeta production. Conversely, a drug that activated S1R triggered an increase in beta secretase cleavage of palAPP and increased production of amyloid beta in axons.”
https://www.massgeneral.org/news/press-release/study-solves-mystery-of-how-amyloid-beta-a-key-player-in-alzheimers-form-%20in-brain-nerve-cells
Here is the snippet from the original paper:
“
Here, we show that downregulating MAM assembly by either RNA silencing or pharmacological modulation of the MAM-resident sigma1 receptor (S1R) leads to attenuated ß-secretase cleavage of palAPP. Upregulation of MAMs promotes trafficking of palAPP to the cell surface, ß-secretase cleavage, and Aß generation. We develop a microfluidic device and use it to show that MAM levels alter Aß generation specifically in neuronal processes and axons, but not in cell bodies. These data suggest therapeutic strategies for reducing axonal release of Aß and attenuating ß-amyloid pathology in AD.”
So it seems Anavex with A2-73 is doing the opposite of what really should be done!!! Fortunately then we might conclude A2-73 is a very good S1R agonist.
Or is it only selectively papers that disagree with my posts that we should rate?
If a Rudolph Tanzi paper is all one’s got it’s not great. But I guess some here now likes his contribution to this more recent paper suggesting silencing the SIGMAR1 gene or blocking the Sigma-1 receptor using a S1R antagonist is a way to treat AD.
“Next, the MGH team wanted to learn what happens when MAM levels and activity were intentionally altered. They showed for the first time that preventing assembly of MAMs, either with gene therapy or a drug that blocked a key protein called the sigma-1 receptor (S1R), dramatically decreased beta secretase cleavage of palAPP in axons and lowered Abeta production. Conversely, a drug that activated S1R triggered an increase in beta secretase cleavage of palAPP and increased production of amyloid beta in axons.”
https://www.massgeneral.org/news/press-release/study-solves-mystery-of-how-amyloid-beta-a-key-player-in-alzheimers-form-%20in-brain-nerve-cells
Here is the snippet from the original paper:
“
Here, we show that downregulating MAM assembly by either RNA silencing or pharmacological modulation of the MAM-resident sigma1 receptor (S1R) leads to attenuated ß-secretase cleavage of palAPP. Upregulation of MAMs promotes trafficking of palAPP to the cell surface, ß-secretase cleavage, and Aß generation. We develop a microfluidic device and use it to show that MAM levels alter Aß generation specifically in neuronal processes and axons, but not in cell bodies. These data suggest therapeutic strategies for reducing axonal release of Aß and attenuating ß-amyloid pathology in AD.”
So it seems Anavex with A2-73 is doing the opposite of what really should be done!!! Fortunately then we might conclude A2-73 is a very good S1R agonist.
Or is it only selectively papers that disagree with my posts that we should rate?
Recent AVXL News
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