Loss of sorting nexin 27
contributes to excitatory synaptic dysfunction by modulating glutamate receptor
recycling in Down's syndrome
"Here we demonstrate a new role for SNX27 in the dysregulation of synaptic function in Down's syndrome. We show that chromosome 21–encoded miR-155 targets and downregulates C/EBPβ, which is a transcription factor for SNX27. Thus, the lower amounts of C/EBPβ in Down's syndrome lead to reduced SNX27 expression. We show that SNX27 promotes recycling of AMPARs and NMDARs from early endosomes to the plasma membrane through direct PDZ binding and thus prevents their degradation. Deletion of Snx27 in mice results in synaptic dysfunction and cognitive deficits. Further, overexpressing Snx27 in the hippocampus of Ts65Dn mice reverses the impairments in receptor amounts and synaptic functions, as well as in hippocampus-dependent memory. Therefore, SNX27 is crucial for maintaining glutamate receptors through post-translational mechanisms and is required for normal synaptic activity and memory formation."Of course, I went looking for a way to increase the expression of SNX 27 and in a matter of days I found it. I love the internet!
In Slesinger Lab at the Salk Institute, they are studying SNX27 and other parts of the signalling pathways. They found that Stimulants up regulated SNX27. I think ADHD meds qualify as a stimulant.
Of course I want to know how we can help our little 1 year old Down Syndrome Lizzie. What are you doing?
ReplyDeleteHi, Teresa!
ReplyDeleteCan you give us more details? Do you think that meds like Ritalin, Adderall and Dexedrine should reduce cognitive disabilities when taken by people with Down Syndrome? Do you know if there are any tests results about it? Thank you, Natalia.
This comment has been removed by the author.
ReplyDeleteI am very interested to find answer to the same question, how we can probably try to increase SNX27 expression?
ReplyDeleteCould you, please, elaborate on what you've found?
This comment has been removed by the author.
ReplyDeleteHere is the Salk Institute website http://www.salk.edu/labs/slesinger/research_background.php
ReplyDeleteOn this website they explain the connection between the GIRK channels/SNX 27.
I think Ritalin, Focalin and those types of meds are considered stimulants. Adderall is not a stimulant.
For more information please visit www.changingmindsfoundation.net
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ReplyDeleteTeresa,
ReplyDeleteHere is another angle to consider:
http://mentalhealth.about.com/library/sci/1201/blwaste1201.htm
Drs. Buck and Chojkier showed that TNF alpha causes oxidative stress in the liver cell and boosts the production of the free-radical gas nitric oxide. It also causes the addition of a phosphorous molecule to a protein called C/EBP beta, which normally joins DNA in the nucleus of the cell to make other proteins, such as albumin.
This article is about albumin but the point that I want to make is that
inflammation appears to be the cause of the low levels of C/EBP beta and thus also SXN27.
MiRNA-155 is a real problem in Down Syndrome and affects the immune system and increases inflammation.
Central to the researchers' finding was that this extra phosphorous causes the C/EBP beta to shuttle out of the nucleus into the cytoplasm
It also causes the addition of a phosphorous molecule to a protein called C/EBP beta, which normally joins DNA in the nucleus of the cell to make other proteins, such as albumin.
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