Press release: University of Pennsylvania-LED Study set up a new Genetic Risk Factor for Lou Gehrig's disease

PolyQ protein ataxin 2, ALS role mentioned, yeast, fruit flies and human ALS motor neurons.

PHILADELPHIA –-International research led by biologists and the University of Pennsylvania-neurofilosofiaa has identified a new genetic risk factor for als lateral sclerosis (ALS), ALS, or Lou Gehrig disease commonly known.  

Yeast and fruit flies to simple yet fast and powerful as templates, and then, after screening, human DNA, found evidence that the Group ataxin 2 gene mutations, genetic disease, in particular, a participant in the study shows that the execution of the amino acid glutamine-ataxin 2 plug-ins are in risk of als, the ALS cases Investigated 4.7% often.  Results were published in nature this week.

  There is no treatment of ALS and the current processing only slow down the progress of the disease.Ataxin 2 and TDP-43 pathological identification, interaction, the second ALS related to disease maqui berry free trial protein ataxin 2 intermediate, strong length-polyQ plug-ins and ALS, genetic association with the development of biomarkers should support and empower the development of new therapies for this disease.

Research began co-senior author Aaron Gitler Associate Professor of cell and developmental biology Penn's School of Medicine, is the laboratory by identifying the genes that may prevent improve yeast toxicity TDP-43.  Group move to about yeast gene strain was designed yeast explicit human TDP-43. Genes, in which case the modified toxicity among ataxin 2 yeast was the match. 

  Then, in cooperation with Gitler lab Nancy Bonini, Penn's Lucille b. Williams Professor of Biology, investigator, Howard Hughes Medical Institute and author of the co-senior research and transfer of the Management Committee for fresh fruit fly gene genes and their interactions with, in order to assess the impact of diseases of the nervous system.

The results of the investigation, normal value was established as the fruit fly models, biochemical analyses have been carried out and the use of human cells, reveals that effective ataxin 2 is a modifier TDP-43. the investigation showed that the ataxin 2 and TDP-43 interact with animal and cellular models patogeneesiä.

The results of measurements shall be expressed in the field of protein engineering, and a link between the disease.For example, when the researchers aimed at TDP-43 of fruit on the fly when applied to the progressive, the age dependent degeneration began.Motor neurons are directed to when to fly to a loss of experienced business gradually. the higher the levels of ataxin 2 TDP-43 was higher, the result is a more severe toxicity of degeneration.Ataxin 2 minus was less toxicity.

"Ataxin 2 reduction of yeast, which has been able to prevent some TDP-43 toxic effects, because we believe that this may be the subject of new therapeutic ALS" said Gitler.

Researchers extend these conclusions ask if ataxin 2 showed with the ALS Association of indicative changes. Teaming Penn Medicine John Trojanowski and Virginia Lee, they found that ataxin 2 appeared ALS patients impacted by spinal cord neurons. Following this analysis, mutation, that can be found on the ataxin 2 other diseases, spinocerebellar ataxia 2, or the extension of polyQ, SCA2, showed, the connection type between the extended ataxin 2 repeats and risk als. in order to limit the risk of als plug-ins were shorter than they are, but more than the controls in the SCA2.

Ataxin 2 gene was previously profitable, the other neurodegenerative disease spinocerebellar ataxia 2 or Ataxin 2 SCA2. contains duplicate user charge the amino acid Glutamine, condensed (q). This is called polyQ, digestive tract is usually short, only about 22 or 23 Qs; however, where there will be an increase of more than 34 polyQ mikrobiston Qs, patients develop SCA2.

New results show that the interval length polyQ delay between 27 and 33 Qs, longer than usual, but shorter than what causes SCA2, increase the ALS.

Michael Hart, Penn graduate student, Gitler's laboratory and co-first investigation "has been a previous tricks similarities ALS and SCA2," said. "Our findings suggest molecular analysis for these similarities and one disease therapies can be an effective, second possibility. "

"Our conclusion is that if you have more 27Qs or to show your own strictly ALS ataxin 2 gene that increases the risk of it," said Gitler.

Before Penn research, Gitler and his team in the past, it was found that the lower TDP-43 yeast in a manner that reflects the ALS Reproduction toxicity and TDP-43 ALS cause mutations do protein clump more quickly, the result is increased toxicity.

Ataxin 2 studies, which show that it may be the cause of neurodegeneration, which previously had been Bonini and his group.

"A novel and potentially common ALS disease gene simple yeast from the screen, we need a greater focus on fruit fly, create a more complex model stresses the yeast and fly an extra power model systems receives information about the human diseases, such as" patogeneesiä Bonini said.

Complementary participants research include Andrew c. Elden, p. Brian Johnson, Xiaodong Fang, Maria Armakola, MIN Min Lu and Arun Padmanabhan Department cell Biology and developmental toxicity, Penn Medicine, Biology Department, School of Arts and Sciences is Penn, Kim Hyung-Jun Felix Geser, Robert Greene, Vivianna m. Van Deerlin and Dana Clay-neurodegenerative diseases research Penn Falcone; Leo McCluskey and neurologian title Penn Medicine, Alice p. Plotkin neurodegenerative diseases Chen and neurologian title Center; Denise Juhr and Peter j. Gruber children's Hospital of Philadelphia and Udo Rüb and Georg Auburger Goethe University Lauren Elman Center.

Research supported by the pilot in the form of a grant of aging, Director's new Innovator Award for health institutes, error correction, Charitable trusts administered by the National Institute of neurological disorders and stroke, National Institute of aging band, Burroughs Wellcome Fund is the career development Award, Deutsche Heredo-Ataxie-Gesellschaft Spinocerebellar Ataxias, and The Deutsche Forschungsgemeinschaft Integrated Project Institute in computer science from the University of Pennsylvania.