I work in Professor Peter Andersen's research group and my research is focused on the Motor Neuron Disease - Amyotrophic lateral sclerosis (ALS)
I work in Professor Peter Andersen's research group and our research is focused on amyotrophic lateral sclerosis (ALS), which is a common term for a group of motor neuron diseases. I am responsible for the Andersen ALS research laboratory within the Translational Research Center (TRC) and the ALS Research Umeå Consortium - one of the world-leading study centers for SOD1-mediated ALS..
There are several different types of ALS. Common to all subtypes is a progressive degeneration of the motor system that eventually leads to death, usually from respiratory failure. Mutations in the superoxide dismutase type 1 (SOD1) gene can cause SOD1-ALS and are found in 12-23% of all Swedish ALS patients with familial ALS and in 2-5 % of those who have no close relative with the disease, so-called sporadic ALS.
Today more than 200 distinct mutations in SOD1 have been identified in ALS patients. Most mutations make the normal structure of the SOD1 protein less stable and increase the chance that it misfolds into an incorrect structure. Aggregates of misfolded SOD1 are found both in the spinal cord tissue from ALS patients, and in transgenic mice expressing human mutated SOD1. Previous studies show that misfolded SOD1 protein gain a new, toxic function. Our research in transgenic mouse models has also shown that aggregated SOD1 has prion-like properties. A prion-like protein that assumes an incorrect shape can infect other cells and act as a template for misfolding of free SOD1 protein in the infected cells. The same mechanism also seems to occur in other neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
There seems to be a connection between the patient's mutation and the course and aggressiveness of the disease. Some ALS patients can live with the disease for more than a decade, while others survive less than two years after experiencing the first symptoms. Our ongoing studies in cell and transgenic mouse models show that different mutations give rise to different types of SOD1 aggregates and that different aggregate structures can be associated with distinct symptoms and progression rate.
Certain mutations cause the SOD1 protein to lose its enzymatic function. This can lead to increased levels of free superoxide radicals in the cells. The significance for of impaired SOD1 function for development of ALS is another aspect of our attempts to understand the broad spectrum of SOD1-mediated ALS.
