Researchers Uncover Toxic Interaction In Neurons That Leads To Dementia And ALS
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.
The research at Mayo Clinic in Florida was financed by the Mayo Clinic Foundation, National Institutes of Health, and National Institute on Aging, ALS Association, and the Department of Defense.
Source: EurekAlert!, the online, global news service operated by AAAS, the science society
Please use one of the following formats to cite this article in your essay, paper or report:
Clinic, Mayo. "Researchers Uncover Toxic Interaction In Neurons That Leads To Dementia And ALS." Medical News Today. MediLexicon, Intl., 13 Dec. 2012. Web.
26 Jun. 2017. <http://www.medicalnewstoday.com/releases/253889.php>
Clinic, M. (2012, December 13). "Researchers Uncover Toxic Interaction In Neurons That Leads To Dementia And ALS." Medical News Today. Retrieved from
Please note: If no author information is provided, the source is cited instead.
Contact our news editors
For any corrections of factual information, or to contact our editorial team, please see our contact page.
Copyright Medical News Today: Excluding email/sharing services explicitly offered on this website, material published on Medical News Today may not be reproduced, or distributed without the prior written permission of Medilexicon International Ltd. Please contact us for further details.