The study, conducted in the laboratory of Don Cleveland, Ph.D., UCSD Professor of Medicine, Neurosciences and Cellular and Molecular Medicine and member of the Ludwig Institute for Cancer Research, will appear in the advance online publication on Nature Neuroscience's website on February 3rd.
“Mutant genes that cause ALS are expressed widely, not just in the motor neurons,” Cleveland explained. “Targeting the partner cells like astrocytes, which live in a synergistic environment with the neuron cells, helps stop the ‘cascade of damage.’ Therapeutically, this is the big news.”
ALS is a progressive disease that attacks the motor neurons, long and complex nerve cells that reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body, which act to control voluntary movement. Degeneration of the motor neurons in ALS leads to progressive loss of muscle control, paralysis and untimely death. Estimated to affect some 30,000 Americans, most people are diagnosed with ALS between the ages of 45 and 65. Typically, ALS patients live only one to five years after initial diagnosis.
In findings published in Science in June 2006, Cleveland and his colleagues showed that in early stages of inherited ALS, small immune cells called microglia are damaged by mutations in the SOD1 protein, and that these immune cells then act to significantly accelerate the degeneration of the motor neurons. The new study demonstrates that much the same thing happens to astrocytes, support cells that are essential to neuronal function, and whose dysfunction is implicated in many diseases. The researchers speculate that the non-neuronal cells play a vital role in nourishing the motor neurons and in scavenging toxins from the cellular environment. As with microglia, the helper role of astrocytes is altered due to mutations in the SOD1 protein.
“We tested what would happen if we removed the mutant gene from astrocytes in mouse models,” said Cleveland. “What happened was it doubled the lifespan of the mouse after the onset of ALS.”
Astrocytes are key components in balancing the neurotransmitter signals that neurons use to communicate. To examine whether mutant SOD1 damage to the astrocytes contributes to disease progression in ALS, researchers in the Cleveland lab used a genetic trick to excise the mutant SOD1 gene, but only in astrocytes. Reduction of the disease-causing mutant SOD1 in astrocytes did not slow disease onset or early disease; however, the late stage of the disease was extended, nearly doubling the normal life expectancy of a mouse with ALS.
“Silencing the mutant gene in the astrocytes not only helps protect the motor neuron, but delays activation of mutant microglia that act to accelerate the progression of ALS,” said Cleveland.
The findings show that mutant astrocytes are likely to be viable targets to slow the rate of disease spread and extend the life of patients with ALS. Cleveland added that this may prove especially important news to researchers in California and elsewhere working with stem cells. “This gives scientists a good idea of what cells should be replaced using stem cell therapy. Astrocytes are very likely much easier to replace than the slow-growing motor neuron.”
Debra Kain | EurekAlert!
Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign
Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
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
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences