In the short space of three months, details of a second gene have been published linking MND to the protein recycling system in our cells.
Leading this research was Prof Teepu Siddique, eminent MND researcher from North Western University in Chicago USA. Not only was he the founder of the first MND causing gene SOD1, but he also led the group that identified faults in the UBQLN2 gene in MND in August 2011. This research was published in the November edition of the Archives of Neurology journal.
We’ve invited Prof Siddique to give a plenary talk at this year’s International Symposium in Sydney, Australia from 30 November to 2 December 2011, at which we believe he’ll be discussing these exciting new advances!
What did they do?
Instead of searching for common genetic mistakes in families with the inherited form of MND, this research group focused on a candidate gene called SQSTM1. They chose SQSTM1 as a candidate due to the prior knowledge that its protein product is associated with MND.
They then unravelled the code for this particular gene in 340 people with the rare, inherited form of the disease and 206 sporadic cases of MND. They also compared these with 738 healthy controls.
They identified 10 different mistakes in the SQSTM1 gene in 15 people and did not find any of these mistakes in the healthy controls. The research group therefore estimate that genetic mistakes in the SQSTM1 gene could account for approximately 2-3% of cases of MND.
However, it is not yet conclusively known whether these mistakes cause MND, or increase the risk of somebody developing the disease. Further studies are therefore needed to confirm this.
What does SQSTM1 do?
The gene SQSTM1, holds the instructions for a protein called P62, otherwise known as sequestosome 1.
The P62 protein can be thought of as a ‘bounty hunter’ of proteins that need to be recycled inside motor neurones and other cells. When given instructions to find proteins waiting to be recycled, it seeks them out and delivers them to the cells recycling system.
P62 has a related role to ubiquilin 2 (UBQLN2 which we wrote about in August) as they both work in the protein recycling system within the body.
This research therefore further implicates that the protein recycling system is faulty in MND.
The next steps with this story, is for researchers to confirm whether mistakes in the SQSTM1 gene cause, or contribute to the disease in other populations around the world. They will also need to investigate how the protein recycling system can go wrong in MND to be able to develop new treatments that can target these processes to slow down, or stop the disease.
More information on the protein recycling system:
Last month, Prof John Mayer from University of Nottingham, who is the Chair of our Biomedical Research Advisory Panel, took us behind the scenes of the protein recycling system on our research blog
Read our press release.
Reference: Fecto F et al. Arch Neurol. 2011; 68(11):1-7