Mice with ALS-like Disease Function Better and Live Longer When Protein Receptor’s Activity Is Reduced

Mice with ALS-like Disease Function Better and Live Longer When Protein Receptor’s Activity Is Reduced

Researchers have slowed the progression of an ALS-like disease in mice, and prolonged their lives, by reducing the activity of a protein receptor that helps transmit signals between nerve cells.

The study, which involved the metabotropic glutamate receptor 5, or mGluR5, was published in the journal Neuropharmacology. The article was titled “In-vivo effects of knocking-down metabotropic glutamate receptor 5 in the SOD1G93A mouse model of amyotrophic lateral sclerosis.

ALS is caused by loss of motor neurons, or nerve cells that control muscles. Scientists are uncertain what causes them to die. But one possibility is neurotoxicity, or over-stimulation of motor neurons by  substances such as neurotransmitter glutamates, which carry signals between nerve cells.

MGluR5 is a protein found on the surface of neurons. It occurs at the neurons’ synapses, or junctions between the cells where the transmission of signals takes place.

The function of the protein, which is found on neurons in specific parts of the brain, is to take up glutamate and increase the synapse’s excitability, or responsiveness.

Researchers halved the activity of mGluR5 receptors in mice with an ALS-like disease by breeding out of the animals one of two genes that code for the mGluR5 protein. This led to a more normal glutamate release in the mice’s spinal cords.

Signs of amyotrophic lateral sclerosis appeared later in the mice, and the animals survived longer than mice whose mGluR5 activity was not reduced.

In addition, more motor neurons remained healthy and survived in the mice with the diminished mGluR5 activity. And two kinds of brain cells, astrocytes and microglia, which the body activates when the brain experiences injury, showed less activity in the test mice than in the untreated mice.

Another thing that researchers discovered in the mice with half the mGluR5 activity was less calcium in the cytoplasm of the animals’ neuron cells. Calcium plays a role in transmitting signals between neurons.

The movement functioning of the male mice improved, although in the females it did not, researchers said.

The same group of researchers obtained similar, but less striking, results when they halved the expression of a related glutamate receptor, mGluR1, in mice with ALS. That finding led to a different article, “Knocking down metabotropic glutamate receptor 1 improves survival and disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis.”

“The present results obtained by reducing mGluR5 expression in the mouse model of ALS, along with previous evidence targeting mGluR1, emphasize the role of Group I mGluRs in the development of ALS and allows proposing the hyper activation of these Glu receptors as a novel mechanism contributing to the disease progression,” the researchers wrote.

“The reduced expression of mGluR5 determined delayed clinical onset of the disease, amelioration of symptoms, MN (motor neuron) preservation, and improved biochemical and functional readouts. Our results suggest that pharmacological treatments aimed at blocking Group I mGluRs can reasonably turn out to be effective in counteracting ALS.”

Janet Stewart is a life sciences writer and editor, who completed both PhD course work and oral examinations in the Department of Microbiology and Immunology at McGill University, and holds an M.Sc. in Virology and Immunology.
Janet Stewart is a life sciences writer and editor, who completed both PhD course work and oral examinations in the Department of Microbiology and Immunology at McGill University, and holds an M.Sc. in Virology and Immunology.
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  1. Carol Mongiello says:

    All these different hypothesis. So what’s stopping scientists to try some of these on patients willing try to halt their disease process. Come on now. I’m reading different theories every day. All our medical technology and still no recent developments that may help patients with als. It took Japan to come up with a new drug, after over 20 years here in the good old US of A, nothing. What a pity that our country lacks the knowledge to start to apply some of their theories. THE RIGHT TO TRY ACT may be able to help some willing to try something or anything as their motor functions disappear and they are unable to do the simple things we all take for granted. Imagine having a fly on the tip of your nose. Buzzing away yet you are unable to do anything about it because you are unable to raise your arms. Please start to show the world that behind your theory there is a possible treatment for this devastating disease. Thank you FDA for at least approving Radicava and making it available to all those with als. Frankie’s Mom.

    • Colorado 18yr ALS research shows this article on proteins is light years behind. And Radicava is nothing but big pharma hype. Colorado ALS Research by establishing a link to Alzheimers shows medicine is light years behind ending either. And this is not going to change because getting paid very well to fail 100% in ALS research is a flawed system. Lots of fifeten minutes of fame stories but no recovery methodology. Colorado ALS research shows why veterans are twice as likely to be ALS diagnosed regardless of war served. Ninety percent diagnosed with ALS carry no gene for it. Looking at ANY genetic “signposts” of ALS when ninety percent diagnosed carry no gene is pure desperation. We as mammals “trigger” ALS unknowingly. ALS then in a domino effect becomes a plethora of problems not as disease but as a protein structural “injury” to the body. Progression is stopped in one month with recovery in four to eight months. This project was not funded. It paid it’s own way. And big pharma doesn’t want it. Every Congressman on the hill has been contacted and also Mike Pence. None have responded. This a flawed system. This research can now walk Dwight Clark through the recovery of ALS based on biochemical physics not medicine’s failures. This is Dwight’s call. That is all. DRH

      • Colorado18yr ALS research shows the sooner Maria Shriver and her family get on board with this project the faster their father starts his recovery from Alzheimers. Out of the box thinking doesn’t stay in well paid comfort zones of 100% failure. That is why it succeeds. Look at my followers on Twitter. 1854R. I’ve earned them not bought them. This research has walked the walk and used it’s own assets to accomplished this. And no one in science medicine wants it because it doesn’t conform to big pharma’s drug programs. ALS and Alzheimers are far too complex for a one drug target magic bullet viable recovery methodology. And all of these so called experts are light years behind this project. Know that. DRH

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