Culprits behind ALS and dementia share common pathway

London, October 1 (ANI): Though the two proteins previously found to contribute to ALS have divergent roles, a common pathway links them.

This is according to a new study, led by researchers at the Department of Cellular and Molecular Medicine at the University of California, San Diego School of Medicine.

The discovery reveals a small set of target genes that could be used to measure the health of motor neurons, and provides a useful tool for development of new pharmaceuticals to treat the devastating disorder, which currently has no treatment or cure.

ALS, also known as Lou Gehrig's disease, is an adult-onset neurodegenerative disorder characterized by premature degeneration of motor neurons, resulting in a progressive, fatal paralysis in patients.

The two proteins that contribute to the disease - FUS/TLS and TDP-43 - bind to ribonucleic acid (RNA), intermediate molecules that translate genetic information from DNA to proteins.

In normal cells, both TDP-43 and FUS/TLS are found in the nucleus where they help maintain proper levels of RNA. In the majority of ALS patients, however, these proteins instead accumulate in the cell's cytoplasm - the liquid that separates the nucleus from the outer membrane, and thus are excluded from the nucleus, which prevents them from performing their normal duties.

Since the proteins are in the wrong location in the cell, they are unable to perform their normal function, according to the study's lead authors, Kasey R. Hutt, Clotilde Lagier-Tourenne and Magdalini Polymenidou.

"In diseased motor neurons where TDP-43 is cleared from the nucleus and forms cytoplasmic aggregates," the researchers wrote, "we saw lower protein levels of three genes regulated by TDP-43 and FUS/TLS. We predicted that this, based on our mouse studies, and found the same results in neurons derived from human embryonic stem cells."

In 2011, this team of UC San Diego scientists discovered that more than one-third of the genes in the brains of mice are direct targets of TDP-43, affecting the functions of these genes. In the new study, they compared the impact of the FUS/TLS protein to that of TDP-43, hoping to find a large target overlap.

"Surprisingly, instead we saw a relatively small overlap, and the common RNA targets genes contained exceptionally long introns, or non-coding segments. The set is comprised of genes that are important for synapse function," said principal investigator Gene Yeo, PhD, assistant professor in the Department of Cellular and Molecular Medicine and the Institute for Genomic Medicine at UC San Diego and a visiting professor at the Molecular Engineering Laboratory in Singapore.

See the article here:
Culprits behind ALS and dementia share common pathway