OHSU discovery may lead to new treatment for ALS

July 18, 2012

Researchers at Oregon Health & Science University School of Dentistry have discovered that TDP-43, a protein strongly linked to ALS (Amyotrophic Lateral Sclerosis) and other neurodegenerative diseases, appears to activate a variety of different molecular pathways when genetically manipulated. The findings have implications for understanding and possibly treating ALS and neurodegenerative diseases such as Alzheimer's and Parkinson's.

ALS affects two in 100,000 adults in the United States annually and the prognosis for patients is grim.The new discovery is published online in G3: Genes, Genomes, Genetics (and the July 2012 print issue of G3).

Using a fruit fly model, the OHSU team genetically increased or eliminated TDP-43 to study its effect on the central nervous system. By using massively parallel sequencing methods to profile the expression of genes in the central nervous system, the team found that the loss of TDP-43 results in widespread gene activation and altered splicing, much of which is reversed by rescue of TDP-43 expression. Although previous studies have implicated both absence and over expression of TDP-43 in ALS, the OHSU study showed little overlap in the gene expression between these two manipulations, suggesting that the bulk of the genes affected are different.

"Our data suggest that TDP-43 plays a role in synaptic transmission, synaptic release and endocytosis," said Dennis Hazelett, Ph.D., lead author of the study. "We also uncovered a potential novel regulation of several pathways, many targets of which appear to be conserved."

Explore further: Disease progression halted in rat model of Lou Gehrig's disease

Related Stories

Disease progression halted in rat model of Lou Gehrig's disease

December 12, 2011
Amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig's disease) is an incurable adult neurodegenerative disorder that progresses to paralysis and death. Genetic mutations are the cause of disease in 5% of patients ...

Potential new drug target in Lou Gehrig's disease

November 14, 2011
Two proteins conspire to promote a lethal neurological disease, according to a study published online this week in the Journal of Experimental Medicine.

Recommended for you

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders

August 16, 2017
Northwestern Medicine scientists have demonstrated a new method of analyzing non-coding regions of DNA in neurons, which may help to pinpoint which genetic variants are most important to the development of schizophrenia and ...

Evolved masculine and feminine behaviors can be inherited from social environment

August 15, 2017
The different ways men and women behave, passed down from generation to generation, can be inherited from our social environment - not just from genes, experts have suggested.

Attitudes on human genome editing vary, but all agree conversation is necessary

August 10, 2017
In early August 2017, an international team of scientists announced they had successfully edited the DNA of human embryos. As people process the political, moral and regulatory issues of the technology—which nudges us closer ...

Two genes help older brain gain new cells

August 10, 2017
Two genes act as molecular midwives to the birth of neurons in adult mammals and when inactivated in mice cause symptoms of Fragile X Syndrome, a major cause of mental retardation, a new Yale University study has shown.

New technique searches 'dark genome' for disease mutations

August 10, 2017
When doctors can't find a diagnosis for patient's disease, they turn to genetic detectives. Equipped with genomic sequencing technologies available for less than 10 years, these sleuths now routinely search through a patient's ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.