The neuron-specific isoform of GSK-3beta is required for axon growth.

The neuron-specific isoform of GSK-3beta is required for axon growth.

J Neurochem. 2010 Jan 12;

Authors: Castaño Z, Gordon-Weeks PR, Kypta RM

ABSTRACT Glycogen synthase kinase-3 (GSK-3) has become an important target for the treatment of mood disorders and neurodegenerative disease. It comprises three enzymes, GSK-3alpha, beta and the neuron-specific isoform, beta2. GSK-3 regulates axon growth by phosphorylating microtubule-associated proteins including Tau. A genetic polymorphism that leads to an increase in the ratio of GSK-3beta1 to GSK-3beta2 interacts with Tau haplotypes to modify disease risk in Parkinson's and Alzheimer's disease. We have examined the roles of each isoform of GSK-3 in neurons. Silencing of GSK-3beta2 inhibited retinoic acid-induced neurite outgrowth in SH-SY5Y neuroblastoma cells and axon growth in rat cortical neurons. Inhibition of neurite outgrowth was prevented by co-expression of GSK-3beta2 but not by co-expression of GSK-3alpha or GSK-3beta1. Ectopic expression GSK-3beta2 enhanced the effects of retinoic acid on neurite length and induced neurite formation in the absence of retinoic acid. GSK-3beta2 phosphorylated Tau at a subset of those sites phosphorylated by GSK-3beta1. In addition, Axin, which regulates responses to Wnt signals, associated more readily with GSK-3beta1 than with GSK-3beta2. Our results suggest that GSK-3 inhibitors that target the Axin-binding site in GSK-3 will preserve the beneficial effects of GSK-3beta2 on axon growth.

PMID: 20067585 [PubMed - as supplied by publisher]

Read the complete post at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=20067585&dopt=Abstract

Posted 14 Jan 2010 4:00 AM by pubmed: neuroblastoma
Filed under:

Seten amet diorl oprta ahsellu miokiste porta.

Bean nonumy hendrit mauris phelus porta. Fusce suscipit varius ui. Fusce feugiat malesada odio. Morbi nunc odio, gravida sit cursusnec, luctus aorem. auris phelus porta ae. Fusce suscipit varius ui. Fusce feug.

Read More

There is nothing quite as devastating as hearing that word - neuroblastoma. In seconds your world is turned upside down and your normal life is but a distant memory. You are thrust into a confusing world full of fear. Your child has cancer.

We know. We have been there. The Neuroblastoma Foundation is here for you.

Welcome to our website. It is a place for you to find answers and ask questions. One of the primary goals of the Neuroblastoma Foundation is to ensure that parents, patients and health care professionals find the information they need to make the best treatment decisions possible for children and adults affected by neuroblastoma. There is a vast amount of information throughout the internet, much of which is encapsulated in medical jargon that is so complex that even many medical professionals have difficulty in interpreting its meaning. We are here to help to decipher this information and to make sure you (and your oncologist) understand exactly what it means to you. From treatment decisions to side effects we have parents and experts that have experienced it all and are willing to distill it for you.