Researchers reveal how protein mutation is involved in rare brain development disorder

Researchers reveal how protein mutation is involved in rare brain development disorder
Credit: McGill University

Rearing its head in infancy, Christianson Syndrome is a rare disorder whose symptoms include intellectual disability, seizures and difficulty standing or walking. Although it is becoming increasingly diagnosed, with little being known about the neural mechanism behind the disease, therapeutic options for patients remain limited.

Now, researchers at McGill University focusing on the aspect of the disease, have shown for the first time how a specific mutant form of the SLC9A6 encoding gene for the NHE6 affects the ability of neurons to form and strengthen connections. The findings, which the researchers hope could eventually lead to new treatments for patients, are published online in the journal Neurobiology of Disease.

"NHE6 functions like a GPS inside of , helping other proteins navigate to the correct location to allow the neurons to function properly and remodel the connections they form between themselves during learning and memory situations," explains Dr. Anne McKinney, Professor in the Department of Pharmacology and Therapeutics at McGill's Faculty of Medicine and the study's senior author. "This protein regulates pH of the vesicles, which contain the cargo that moves inside the brain cell. It prevents it from becoming too acidic or too alkali. We now show that if this protein loses its function because of a mutation, then other proteins can no longer be sent to the right places, and thus these neurons are unable to properly undergo learning-type mechanisms. Using methods to regulate the pH of the vesicles we can rescue the cargo trafficking and learning of the neuron."

Using mouse models to study the hippocampus

To make their discovery, the researchers grew mouse neurons on a dish, expressing a mutant version of SLC9A6 discovered in patients. Using and electrophysiology they examined changes in appearance of these brain cells as well as how they responded to artificial learning and memory-type stimulations in a dish.

"We found that by attempting to rescue the 'GPS function' of the protein by compensating with other pharmacological agents, we were able to restore at least some of the proper mechanisms to allow other proteins to be trafficked around the cell normally and thus restore their ability to 'learn,'" notes Andy Gao a Ph.D. student in Dr. McKinney's lab and the study's first author.

A hope for potential therapies

The first study to clearly demonstrate that mutations in SLC9A6 can lead to changes in synaptic function that could be related to the cognitive deficits associated with Christianson Syndrome, the researchers hope that these insights will eventually provide more clues as to how to modify the impact of the mutation in order to provide clinical benefit.

"Interestingly enough, other groups are starting to show that the implicated protein is actually expressed less as well in other more common neurodegenerative disorders, such as Parkinson's and Alzheimer's Diseases," notes Dr. McKinney, who is also Associate Dean, Academic Affairs at the Faculty of Medicine. "Through our work, we can start to develop potential therapeutic targets to improve the quality of life, not only for those suffering from Christianson Syndrome, but from other disorders as well where NHE6 is perturbed."


Explore further

Autism gene stunts neurons, but growth can be restored, in mice

More information: Andy Y.L. Gao et al. A Christianson syndrome-linked deletion mutation (Δ287ES288) in SLC9A6 impairs hippocampal neuronal plasticity, Neurobiology of Disease (2019). DOI: 10.1016/j.nbd.2019.104490
Journal information: Neurobiology of Disease

Provided by McGill University
Citation: Researchers reveal how protein mutation is involved in rare brain development disorder (2019, June 28) retrieved 25 August 2019 from https://medicalxpress.com/news/2019-06-reveal-protein-mutation-involved-rare.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
0 shares

Feedback to editors

User comments

Jul 15, 2019

I have been suffering from HIV and Genital Herpes for the past 3 years and 8 months, and ever since then i have been taking series of treatment but there was no improvement until i came across testimonies of Dr TAKUTA on how he has been curing different people from different diseases all over the world, then i contacted him as well. After our conversation he sent me the medicine which i took according to his instructions. When i was done taking the herbal medicine i went for a medical checkup and to my greatest surprise i was cured from Herpes. My heart is so filled with joy. If you are suffering from Herpes or any other disease you can contact Dr TAKUTA today on this Email address: takutaspellalter@gmail.com or WhatsApp him on this Tell.Number +27788634102....

Dr.TAKUTA also cures:
1. HEPATITIS A,B,C
2. HERPES 1/2
3.DIABETES
4.STROKE.
5.STDS and STI
6. MARRIAGE COUNSELLING
7.LOVE SPELL CASTING
8.JOB PROMOTION SPELLS
9.MARITAL PROBLEM
10.MAGIC MONEY SPELLS

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more