Following a major Northwestern Medicine breakthrough that identified a common converging point for all forms of amyotrophic lateral sclerosis (ALS and Lou Gehrig's disease), a new finding from the same scientists further broadens the understanding of why cells in the brain and spinal cord degenerate in the fatal disease.
Less than three months ago, Northwestern research found that the crucial recycling system for cells in the brain and spinal cord was broken in people with ALS. And one mutated gene had a key role. Like a loafing worker, it wasn't doing its job to recycle damaged cells.
Now, scientists have discovered a second faulty gene -- a new loafing worker -- in the same recycling pathway. The finding is reported in Archives of Neurology.
"Now that we have two bad players, it shines more light on this broken pathway," said senior author Teepu Siddique, M.D., the Les Turner ALS Foundation/Herbert C. Wenske Professor of the Davee Department of Neurology and Clinical Neurosciences at Northwestern's Feinberg School and a neurologist at Northwestern Memorial Hospital. "This gives us a clear target to develop drug therapies to try to fix this problem. It strengthens our belief that this broken system is at the heart of ALS."
The new "bad player" is called sequestosome1. The previously identified mutated gene is ubiquilin2. Because these two genes aren't doing their jobs to recycle damaged proteins, those proteins – as well as sequestosome1 and ubiquilin2 -- accumulate abnormally in the motor neurons in the spinal cord and cortical and hippocampal neurons in the brain. The protein accumulations resemble twisted skeins of yarn -- characteristic of ALS -- and cause the degeneration of the neurons.
In the new study, sequestosome1 genetic mutations were identified in 546 ALS patients; 340 with an inherited form of the disease, called familial, and 206 with a non-inherited form of the disease, called sporadic.
About 90 percent of ALS is sporadic and 10 percent is familial. To date, mutations in about 10 genes, several of which were discovered at Northwestern, including SOD1 and ALSIN, account for about 30 percent of classic familial ALS, noted Faisal Fecto, M.D., study lead author and a PhD candidate in neuroscience at Feinberg.
ALS affects an estimated 350,000 people worldwide, including children and adults, with about 50 percent of people dying within three years of its onset. In the motor disease, people progressively lose muscle strength until they become paralyzed and can no longer move, speak, swallow and breathe. ALS/dementia targets the frontal and temporal lobes of the brain, affecting patients' judgment, the ability to understand language and to perform basic tasks like planning what to wear or organizing their day.
The discovery of the breakdown in protein recycling may also have a wider role in other neurodegenerative diseases, particularly the dementias. These include Alzheimer's disease and frontotemporal dementia as well as Parkinson's disease, all of which are characterized by aggregations of proteins, Siddique said. The removal of damaged or misfolded proteins is critical for optimal cell functioning, he noted.
The study was supported by the National Institute of Neurological Disorders and Stroke, the Les Turner ALS Foundation, the Herbert and Florence C. Wenske Foundation and other sources.
Marla Paul | EurekAlert!
Inactivate vaccines faster and more effectively using electron beams
23.03.2017 | Fraunhofer-Institut für Organische Elektronik, Elektronenstrahl- und Plasmatechnik FEP
Hunting pathogens at full force
22.03.2017 | Helmholtz-Zentrum für Infektionsforschung
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
23.03.2017 | Health and Medicine
23.03.2017 | Physics and Astronomy
22.03.2017 | Materials Sciences