OHSU discovery may lead to new treatment for ALS

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."

add to favorites email to friend print save as pdf

Related Stories

More genes for Lou Gehrig's disease identified

Apr 07, 2008

In recent months a spate of mutations have been found in a disease protein called TDP-43 that is implicated in two neurodegenerative disorders: amyotrophic lateral sclerosis (ALS), also called Lou Gehrig’s disease, and ...

Loss of key protein boosts neuron loss in ALS

Mar 04, 2011

Amyotrophic lateral sclerosis, known as ALS or more popularly, Lou Gehrig's disease, is a notorious neurodegenerative condition characterized by the progressive deterioration of brain and spinal cord neurons, resulting in ...

Recommended for you

Mutation disables innate immune system

9 hours ago

A Ludwig Maximilian University of Munich team has shown that defects in the JAGN1 gene inhibit the function of a specific type of white blood cells, and account for a rare congenital immune deficiency that ...

Study identifies genetic change in autism-related gene

Aug 28, 2014

A new study from Bradley Hospital has identified a genetic change in a recently identified autism-associated gene, which may provide further insight into the causes of autism. The study, now published online in the Journal of ...

NIH issues finalized policy on genomic data sharing

Aug 27, 2014

The National Institutes of Health has issued a final NIH Genomic Data Sharing (GDS) policy to promote data sharing as a way to speed the translation of data into knowledge, products and procedures that improve health while ...

The genes behind the guardians of the airways

Aug 27, 2014

Dysfunctions in cilia, tiny hair-like structures that protrude from the surface of cells, are responsible for a number of human diseases. However the genes involved in making cilia have remained largely elusive. ...

User comments