Instructions on top of the genetic information: what did we learn for MSA?
The current absence of treatments to halt or delay the progression of multiple system atrophy (MSA), and other neurodegenerative diseases, is a major driving force for what we do as researchers.
What do we know?
In MSA and Parkinson’s disease, lumps of a sticky protein called alpha-synuclein form in brain cells, leading to death of nerve cells. The reasons for this are not fully understood.
Proteins are essential for cells because they perform the “chores” and keep them healthy. Several instructions are needed to get the right proteins and amounts. DNA provides the script, a same sequence of letters in all cells of the body, for different proteins to be made. Additional instructions are given by chemical modifications to the DNA, including DNA methylation, which works like a switch to turn on/off the production of the messenger molecule (RNA) and achieve appropriate amounts of each protein in each cell type (nerve or blood cell, for example).
What have we learned about MSA with our recent research at Queen Square Brain Bank?
DNA methylation seems to be important in neurodegenerative diseases. Our recent MSA study revealed considerable differences in DNA methylation levels between MSA and healthy brain tissue (details here). A major finding pointed to a protein called MOBP, which makes part of the myelin, an insulating layer that forms around nerves, allowing electrical impulses to transmit quickly and efficiently along nerve cells. We also found that there is less RNA to make MOBP protein in MSA (details here). Although MOBP had not been linked to MSA before defects in the myelin have, and our studies provided new knowledge about what could be contributing to this. The importance of DNA methylation in MSA has also been shown by others (details here), suggesting its involvement in inflammatory reactions occurring in MSA brains, which we then confirmed in our data (details here).
Because DNA methylation is potentially reversible with appropriate drugs, knowing where the damage occurs is important. With the support from our funders, including the MSA Trust, we have pursued and will continue to pursue this line of research to learn more about MSA, and help improving diagnosis, aid the development of biomarkers and find possible targets for treatment.
By Dr Conceição Bettencourt, Research Fellow at Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology
Disclaimer: The views and opinions expressed in the blogs published on these pages are those of the authors and do not necessarily reflect the official policy or position of the MSA Trust.