Researchers at Mayo Clinic in Florida have uncovered a toxic cellular process by which a protein that maintains the health of neurons becomes deficient and can lead to dementia. The findings shed new light on the link between culprits implicated in two devastating neurological diseases: and amyotrophic lateral sclerosis, also known as Lou Gehrig's disease. The study is published Dec. 10 in the online issue of Proceedings of the National Academy of Sciences.
There is no cure for frontotemporal dementia, a disorder that affects personality, behavior and language and is second only to Alzheimer's disease as the most common form of early-onset dementia. While much research is devoted to understanding the role of each defective protein in these diseases, the team at Mayo Clinic took a new approach to examine the interplay between TDP-43, a protein that regulates messenger ribonucleic acid (mRNA) — biological molecules that carry the information of genes and are used by cells to guide protein synthesis — and sortilin, which regulates the protein progranulin.
"We sought to investigate how TDP-43 regulates the levels of the protein progranulin, given that extreme progranulin levels at either end of the spectrum, too low or too high, can respectively lead to neurodegeneration or cancer," says the study's lead investigator, Mercedes Prudencio, Ph.D., a neuroscientist at the Mayo Clinic campus in Florida.
The neuroscientists found that a lack of the protein TDP-43, long implicated in frontotemporal dementia and amyotrophic lateral sclerosis, leads to elevated levels of defective sortilin mRNA. The research team is the first to identify significantly elevated levels of the defective sortilin mRNA in autopsied human brain tissue of frontotemporal dementia/TDP cases, the most common subtype of the disease.
"We found a lack of TDP-43 disrupts the cellular process called mRNA splicing that precedes protein synthesis, resulting in the generation of a defective sortilin protein," Dr. Prudencio says. "More important, the defective sortilin binds to progranulin and as a result deprives neurons of progranulin's protective effects that stave off the cell death associated with disease."
By improving the scientific community's understanding of the biological processes leading to frontotemporal dementia, the researchers have also paved the way for the development of new therapies to prevent or combat the disease, says Leonard Petrucelli, Ph.D., chair of the Department of Neuroscience at Mayo Clinic in Florida, who led the research.
Mayo Clinic: http://www.mayoclinic.org/news
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
With funding from the Defense Department, scientists have begun work on devices that would use electric pulses to realign a memory process gone awry
On Friday, the Food and Drug Administration released a vital set of numbers about the routine use of antibiotics …
Side order of veg with that mammoth leg? The Neanderthal diet was probably more varied than we think – using vegetables, herbs and different cooking techniques
An exoskeleton that enables movement and provides tactile feedback has helped eight paralysed people regain sensation and move previously paralysed muscles
A female western gray whale set a new record swimming from Russia to Mexico and back, a total of 13,988 miles, in 172 days
Scientists operating a remote-controlled vehicle about 2,000 feet below water get a rare glimpse of a sperm whale. CBSN's Vladimir Duthiers and Elaine Quijano report on the video.
According to the experts, "blinking is like a kitty kiss"
Genetic profiling of cancer cells can help guide treatment, but such profiles can be ambiguous. Results would be more accurate if all labs tested normal cells from each patient, too.
Researchers in Kenya uncover tools dated to 3.3 million years ago, long before the first humans, as we know them, walked the Earth.
Researchers are facing up to methodological flaws that plague functional magnetic resonance imaging, but the interpretative problems might be harder to solve