Skip to main content

Posts

Showing posts from April, 2017

Zinc, Hedgehog Signaling, Shank2/3, NMDA/AMPA Inactivation and Autism

I am gradually tying up the loose ends in this blog. Today several issues are dealt with that are all connected by zinc. Some are extremely complicated and I will skip over the details.


Not that kind of hedgehog

1.In those rather complicated graphics in the literature that explain signaling pathways, you may have noticed something called hedgehog signaling. This is a basic pathway present in all bilaterians - creatures with a head and tail/feet and a left and right. So flies, yes; but jelly fish, no.In autism there is excessive hedgehog signaling.Zinc deficiency is linked to activation of the hedgehog signaling pathway
2.One of the commonly used models of autism is called Shank3; there is another one called Shank2.Shank proteins are scaffold proteins that connect neurotransmitter receptors and ion channels to the actin cytoskeleton and G-protein-coupled signaling pathways.Mutations in these genes are associated with autism. This gets very complicated.
3.In trying to consider all types of …

The Excitatory/Inhibitory Imbalance � GABAA stabilization via IP3R

This blog aims to synthesize the relevant parts of the research and make connections that point towards some potential therapeutic avenues.Most researchers work in splendid isolation and concentrate on one extremely narrow area of interest.
The GABAA reset, not functional in some autism
On the one hand things are very simple, if the GABAAreceptors function correctly and are inhibitory and the glutamate receptors (particularly NMDA and mGluRx) function correctly, there is harmony and a perfect excitatory/inhibitory balance.
Unfortunately numerous different things can go wrong and you could write a book about each one.
As you dig deeper you see that the sub-unit make-up of GABAAreceptors is not only critical but changes.The plus side is that you can influence this.
Today we see that the receptors themselves are physically movable and sometimes get stuck in the �wrong place�. When the receptors cluster close together they produce a strong inhibitory effect, but continual activation of NMDA re…