Mu​tated genes and proteins in ALS/MND

This project will look at a particular gene and how changes in the gene (called mutations) react with proteins which help protect motor neurones.

Background

Amyotrophic lateral sclerosis (ALS) is a type of MND, which stop signals from the brain reaching the muscles, resulting in a progressive loss of all muscle functions. Many patients also show signs of cognitive problems, which in around 20-50% of cases fulfil the diagnostic criteria of a type of dementia; frontotemporal dementia (FTD).

In 2011 mistakes (mutations) in a gene called Ubiquilin-2 were found to cause ALS/FTD, but it was not known how or why these mistakes lead to disease. Dr Kurz has recently discovered that mutation to this gene means that material that normally would be removed from the cell (“garbage disposal”) accumulates and forms clumps, which eventually leads to cell death.

Along with this discovery, researchers have also made several interesting preliminary observations, which likely contribute to the development of ALS.

The project

The research team found that mutated Ubiquilin-2 genes interact differently with two other proteins (Bag6 and Trim32). These proteins are also involved in the cell’s “garbage disposal” process and these changes in interaction are likely to be important.

Researchers also found that mutated Ubiquilin-2 genes behave differently in a certain region of the brain.

The aims of this project are:

  • to identify how Ubiquilin-2 functions with the proteins Bag6 and Trim32 and;
  • to shed light on how these functions are affected in ALS/FTD
  • to determine why Ubiquilin-2 behaves differently in a certain region of the brain and how this is connected to ALS/FTD.

 

Find out more

For more information please contact:

Thimo.Kurz@glasgow.ac.uk

Project title: Defining the molecular functions of the ALS/MND gene Ubiquilin-2 (UBQLN). Please see MND Scotland's Animal Testing Policy.

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“MND Scotland supports research in my laboratory to understand the underlying causes of Motor Neurone Disease. Our efforts are aimed at delineating how mutations in certain genes cause inherited MND. This work will allow us to understand what goes wrong in the nerve cells of patients, with the hope that this will also be applicable to non-inherited cases of MND. In order to develop treatments in the future, we need to understand the molecular details of this devastating disease, and the support of MND Scotland is vital to achieving this goal.”

Dr. Thimo Kurz

Dr. Thimo Kurz