Scientists at Northwestern University report a surprising discovery that offers a possible new route for the treatment of neurodegenerative diseases. In a study of the transparent roundworm C. elegans, they found that a genetic switch in master neurons inhibits the proper functioning of protective cell stress responses, leading to the accumulation of misfolded and damaged proteins.
Neurodegenerative diseases, ranging from Huntington's and Parkinson's to amyotrophic lateral sclerosis and Alzheimer's, are believed to stem from early events that lead to an accumulation of damaged proteins in cells. Yet all animals, including humans, have an ancient and very powerful mechanism for detecting and responding to such damage, known as the heat shock response.
"Why are these diseases so widespread if our cells have ways to detect and prevent damaged proteins from accumulating?" said Richard I. Morimoto, who led the research together with postdoctoral colleague Veena Prahlad. "Can our body fix the problem? That is the conundrum."
"In our study, much to our surprise, we discovered that the nervous system sends negative signals to other tissues in the animal that inhibit the ability of cells to activate a protective heat shock response," Morimoto said. "The machinery to repair the damaged proteins is intact, but the nervous system is sending a signal that prevents it from doing its job."
When the signal from the nervous system was reduced, the cells' heat shock response returned, leading to elevated levels of special protective proteins, called molecular chaperones, that kept the damaged proteins in check.
Morimoto is the Bill and Gayle Cook Professor of Biology in the department of molecular biosciences and the Rice Institute for Biomedical Research in Northwestern's Weinberg College of Arts and Sciences.
The findings are published by the Proceedings of the National Academy of Sciences (PNAS).
"Currently, we have no solution for these devastating diseases," Morimoto said. "This master neuronal switch could offer a new target for therapy. If we can restore the natural ability of cells to prevent protein damage, our cells should be healthier longer and the quality of life will be better."
The findings are also applicable to other diseases that involve protein misfolding, such as cancer and metabolic diseases, Morimoto said.
Morimoto and Prahlad studied C. elegans, specifically models with different forms of protein misfolding diseases. The transparent roundworm is a valued research tool as its biochemical environment is similar to that of human beings and its genome, or complete genetic sequence, is known.
They interfered with the nervous system signal, the "master switch," to see what would happen to the animals. When the signal was working, the animals accumulated damaged proteins in their cells that interfered with cellular function. But when the researchers reduced the neuronal signal a little bit, the normal cellular response to protein damage returned and the animals were healthy.
While the downregulation of the neuronal signal in the study was done genetically, in humans the idea would be to alter the signal chemically, Morimoto said.
"This work gives us an appreciation that animals are not just a bundle of cells, each on its own to sense and respond to damage," he said. "The cells are organized into tissues, tied into a network that is organized by the brain. The brain can tell the cells to turn on a stress response or not. The nervous system is talking to all the parts to orchestrate an organismal response to stress. That's what's so fascinating."
The paper, titled "Neuronal circuitry regulates Q:1 the response of Caenorhabditis elegans to misfolded proteins," is available at http://www.pnas.org/content/early/2011/08/10/1106557108.abstract.
Megan Fellman | EurekAlert!
Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)
CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy