Another recycling bounty hunter linked to MND

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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

5 thoughts on “Another recycling bounty hunter linked to MND

  1. Another brilliant article Kelly! Thank you. Do you think this has been the most exciting year in research for MND? I’m relatively new to this all (mum diagnosed Sept 2010) but 2011 seems to have been the year for some major advancements in understanding this disease.

    1. Thanks Matt,

      It has indeed been a very exciting year in terms of MND research. I think that’s largely due to advances in genetic technology – the fact that we now know the causative genes for ~70% of cases of familial MND is incredible! It used to be quite simple to recite genes linked to MND using one hand, but now the list is growing ever longer and the picture grows ever more complicated. It’s like being given a 1,000 piece jigsaw, thinking you’re halfway through then having somebody add another 1,000 more pieces to the unfinished puzzle.

      I’ve listed the genes known to be linked to familial MND below with the years that they were published to see the progression so far:

      SOD1 1993
      VAPB 2004
      Angiogenin 2006
      TARDBP-43 (protein named TDP-43) 2008
      FUS 2009
      DAO 2010
      Optineurin 2010
      VCP 2010
      UBQLN2 2011
      C9ORF72 2011
      SQSTM1 2011

      As you can see, in 2010, and 2011 we had three familial genes identified each year – who knows what 2012 will hold, but the future definitely looks bright as we uncover how these cause MND and how we can target these processes to create a treatment.

      But, the year isn’t quite over yet! We’re very excited about the upcoming symposium, which is now less than two weeks away (30 November – 2 December in Sydney, Australia). With three jam packed days of 100 talks, and 245 poster presentations I know that it’ll be a whirlwind of information, and time really does fly at the symposium. Dr Belinda Cupid, our Head of Research will be blogging from the symposium this year to give you the highlights and insights. We’ll try to cover as much as we can that will be of interest to everybody affected by MND.


  2. Looking forward to hopefully more positive news in trying to find a cure for MND.

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