New discovery may block ALS disease process
New Orleans, LA In the first animal model of Amyotrophic Lateral Sclerosis (ALS), developed by Dr. Udai Pandey, Assistant Professor of Genetics at LSU Health Sciences Center New Orleans, Dr. Pandey's lab has found in fruit flies that blocking the abnormal movement of a protein made by a mutated gene called FUS also blocks the disease process. The research is available online in the Advanced Access section of the journal Human Molecular Genetics website, posted on April 12, 2011. It will be published in an upcoming issue of the journal.
The fruit flies were engineered to carry and express a mutated human FUS gene. This mutated FUS gene has been shown to be one of the major causes of both familial and sporadic ALS. In the fruit flies, the resulting neurodegeneration impairs their ability to walk or climb and the defect is also easily visualized in the structure of their eyes. In addition, the flies carrying the defective FUS gene demonstrate hallmarks of the human disease, such as an age-dependent degeneration of neurons, accumulation of abnormal proteins and a decrease in life span.
Also as seen in human ALS patients, the disease-causing FUS protein that's formed from the gene abnormally moves to the cytoplasm rather than staying in the cell nucleus. Dr. Pandey's lab found that blocking this abnormal migration could block the disease process. All these features make the fly model a valuable resource for performing drug screens to identify drugs that could modify the effects of the mutated gene.
"These findings prompt us to look for drugs that can help in keeping the defective FUS protein in the nucleus as a potential therapeutic intervention" notes Pandey. "The fly model is an inexpensive and fast way to study many human diseases such as cancer, Alzheimer's disease and Parkinson's disease. Many basic biological processes are well conserved between humans and fruit flies, and nearly 75% of human disease-causing genes are believed to have a functional partner (homolog) in the fly that makes these small animals a highly tractable model system."
Dr. Pandey's group found that normal FUS interacts with another major human ALS-linked protein TDP-43, but mutated FUS interacts abnormally with normal TDP-43. Mutations in the TDP-43 gene have also been found to cause ALS. Interestingly, these two ALS-linked proteins do not seem to interact if trapped in the nucleus.
According to the National Institutes of Health, Amyotrophic Lateral Sclerosis, sometimes called Lou Gehrig's disease, is a rapidly progressive, invariably fatal neurological disease that attacks the nerve cells (neurons) responsible for controlling voluntary muscles. The disease belongs to a group of disorders known as motor neuron diseases, which are characterized by the gradual degeneration and death of motor neurons. Motor neurons are nerve cells located in the brain, brainstem, and spinal cord that serve as controlling units and vital communication links between the nervous system and the voluntary muscles of the body. Messages from motor neurons in the brain (called upper motor neurons) are transmitted to motor neurons in the spinal cord (called lower motor neurons) and from them to particular muscles. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, waste away (atrophy), and twitch (fasciculations). Eventually, the ability of the brain to start and control voluntary movement is lost.
"Our next goal is to identify other factors such as proteins or RNA that mutant forms of FUS target so that we can get more insights into the disease mechanisms" said Nicholas Lanson Jr., an LSUHSC research associate and first author of the paper.
Provided by Louisiana State University Health Sciences Center
- Researchers discover genetic link between both types of ALS May 05, 2010 | not rated yet | 0
- Lou Gehrig's protein found throughout brain, suggesting effects beyond motor neurons Jun 16, 2008 | not rated yet | 0
- Malfunctioning gene associated with Lou Gehrig's disease leads to nerve-cell death in mice Jan 04, 2011 | not rated yet | 0
- Researchers identify a gene responsible for Lou Gehrig's disease Mar 31, 2008 | not rated yet | 0
- Second MND gene mutation in one year signifies rapid research progress Feb 26, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | not rated yet | 0 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
The use of genome-wide analysis (GWA), where the entirety of an individual's DNA is examined to look for the genomic mutations or variants which can cause health problems is a massively useful technology for diagnosing disease. ...
Genetics May 16, 2013 | not rated yet | 0
DNA databases might help identify victims of crime and human trafficking, but how do we safeguard the personal privacy of innocent victims and family members? A new report online May 15 in the Cell Press journal Trends in ...
Genetics May 15, 2013 | not rated yet | 0
An increasing number of U.S. children are experiencing gastrointestinal issues that require interventions to resolve, according to research presented at Digestive Disease Week (DDW).
10 minutes ago | not rated yet | 0 |
A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...
8 minutes ago | not rated yet | 0
Big names in medicine are set to give an upbeat assessment of the war on AIDS on Tuesday, 30 years after French researchers identified the virus that causes the disease.
8 hours ago | 5 / 5 (1) | 0
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
9 hours ago | not rated yet | 0 |
(Medical Xpress)—What if the quality of your work depends more on your focus on the piano keys or canvas or laptop than your musical or painting or computing skills? If target users can be convinced, they ...
21 hours ago | 3.7 / 5 (3) | 0 |
The neural machinery underlying our olfactory sense continues to be an enigma for neuroscience. A recent review in Neuron seeks to expand traditional ideas about how neurons in the olfactory bulb might encode information about ...
20 hours ago | not rated yet | 0 |