In the Nov. 17 online issue of the American Journal of Human Genetics, the scientists write that they discovered a link between two proteins — progranulin and sortilin — they say might open new avenues for the treatment of frontotemporal lobar degeneration (FTLD), which occurs in the frontal lobe and temporal lobe of the brain.
This form of dementia, which is currently untreatable, generally occurs in younger people, compared to other common neurodegenerative disorders such as Alzheimer's disease.
"We now can look for a direct link between these two proteins and the development of FTLD," says the study's lead author, neuroscientist Rosa Rademakers, Ph.D. "The hope is that if we do find a strong association, it might be possible to manipulate levels of one or both of these proteins therapeutically."
Coincidentally, a research group from Yale University led by Stephen Strittmatter, M.D., Ph.D., has also pinpointed sortilin's association with progranulin — thus confirming Mayo's results. Their study is being published in Neuron, also on Nov. 17.
FTLD is a family of brain diseases that are believed to share some common molecular features. One is the presence of mutations in the gene that produces tau protein in neurons. The other is mutations in the progranulin gene that Mayo Clinic researchers and their colleagues discovered in 2006. They found that 5 to 10 percent of patients with FTLD have a mutation in this gene, and that these mutations lead to a substantial loss of normal progranulin protein production, and development of FTLD.
The protein made by the progranulin gene is found throughout the body, and performs different functions according to the type of tissue (organ) it is located in. But in the brain, it is believed to support neurons and keep them healthy.
Still, researchers do not really know how normal progranulin protein functions in the brain — what other proteins it interacts with — and so in this study they sought to uncover clues about progranulin biology by conducting a genome-wide association study (GWAS).
Based on their previous findings that a simple blood test is able to measure progranulin levels in plasma and could be used to identify patients with progranulin mutations, they tested blood from 518 healthy individuals in a GWAS to look for genetic variants that could explain some of the normal variability of progranulin levels in plasma. They found very strong association with two genetic variants in the same region of chromosome 1 and confirmed this finding in a second group of 495 healthy individuals.
By reviewing the scientific literature, they further ascertained that the same genetic variant found to be associated with plasma progranulin levels also affects the levels of the protein sortilin. Like progranulin, sortilin is found throughout the body and is involved in different tasks. In the brain, it is known to be important for survival of brain neurons.
"So, using a genetic approach, we identified a previously unknown connection between sortilin and progranulin," Dr. Rademakers says.
The researchers then studied the two proteins in cell culture and showed that the amount of sortilin in cells determines how much progranulin is taken inside or remains outside of a cell. "Our study shows that changes in the levels of sortilin result in different levels of progranulin available to cells. Given that we found FTLD patients often have less progranulin than they should, we believe that if you can manipulate levels of progranulin and/or sortilin in the brain, you might have a way to treat this disorder," says Dr. Rademakers.
"Our study and the study led by the Yale researchers describe completely independent and unbiased screens which both identified this protein sortilin as being important in the regulation of progranulin," Dr. Rademakers says. "This obviously opens new avenues for treatment for patients with progranulin mutations and perhaps dementia patients in general."
Researchers from the National Institutes of Health, University College London, the University of British Columbia, and Mayo Clinic in Minnesota also participated in this study.
The study was funded by the National Institutes of Health and the Consortium for Frontotemporal Dementia Research. The authors declare no conflicts of interest.About Mayo Clinic
Kevin Punsky | EurekAlert!
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
26.04.2017 | Materials Sciences
26.04.2017 | Agricultural and Forestry Science
26.04.2017 | Physics and Astronomy