ALS Researchers Uncover New Insights Into Motor Neuron Death in Lou Gehrig’s Disease

ALS Researchers Uncover New Insights Into Motor Neuron Death in Lou Gehrig’s Disease
Posted by: Susan Ardizzoni March 31, 2014

Current research at The Institute at Nationwide Children’s Hospital has revealed information about a key player in motor neuron death in Amyotrophic lateral sclerosis (ALS) otherwise known as Lou Gehrig’s disease. The researchers believe this to be a key step in developing a treatment.

ALS involves a cascade of cellular and inflammatory events that weakens and kill motor neurons in the brain and spinal column. The motor neuron destruction is a complex process that involves cells that normally protect neurons from harm. These motor neurons control the function of muscles throughout the body. As the motor neurons die, muscles begin to weaken. Individuals with ALS eventually lose their ability to move, and with further progression they are unable to breathe on their own. Within 3 to 5 years of onset, most ALS patients die from respiratory failure.

Researchers took a look at a protein that is involved in transcriptional regulation known as nuclear factor-kappa B (NF-κB). This protein is involved with the neuro-inflammatory response that is common in ALS, and it has also been linked to cancer and a number of other inflammatory and autoimmune diseases.

The study examined ALS progression in mice where NF-κB was inhibited in astrocytes and microglia. These two cell types are the first and main form of defense against pathogens in the brain and spinal column. According to Brian Kaspar, MD, a principal investigator in the Center for Gene Therapy at Nationwide Children’s and senior author of the new study, inhibiting NF-κB in microglia decreased ALS progression by 47 percent. “ The field has identified different cell types in addition to motor neurons involved in this disease, so one of our approaches was to find out what weapons these cells might be using to kill motor neurons. And our findings suggest that the microglia utilize an NF-κB-mediated inflammatory response as one of its weapons.”

Researchers report that inhibiting NF-κB in astrocytes had no effect on ALS progression so the search for weapons that astrocytes use against motor neurons still continues. How or why NF-κB causes microglia to turn into neuron-killing agents still remains a mystery, however the current study moves researchers closer to finding therapy for ALS.

Current research at The Institute at Nationwide Children’s Hospital has revealed information about a key player in motor neuron death in Amyotrophic lateral sclerosis (ALS) otherwise known as Lou Gehrig’s disease. The researchers believe this to be a key step in developing a treatment.

ALS involves a cascade of cellular and inflammatory events that weakens and kill motor neurons in the brain and spinal column. The motor neuron destruction is a complex process that involves cells that normally protect neurons from harm. These motor neurons control the function of muscles throughout the body. As the motor neurons die, muscles begin to weaken. Individuals with ALS eventually lose their ability to move, and with further progression they are unable to breathe on their own. Within 3 to 5 years of onset, most ALS patients die from respiratory failure.

Researchers took a look at a protein that is involved in transcriptional regulation known as nuclear factor-kappa B (NF-κB). This protein is involved with the neuro-inflammatory response that is common in ALS, and it has also been linked to cancer and a number of other inflammatory and autoimmune diseases.

The study examined ALS progression in mice where NF-κB was inhibited in astrocytes and microglia. These two cell types are the first and main form of defense against pathogens in the brain and spinal column. According to Brian Kaspar, MD, a principal investigator in the Center for Gene Therapy at Nationwide Children’s and senior author of the new study, inhibiting NF-κB in microglia decreased ALS progression by 47 percent. “ The field has identified different cell types in addition to motor neurons involved in this disease, so one of our approaches was to find out what weapons these cells might be using to kill motor neurons. And our findings suggest that the microglia utilize an NF-κB-mediated inflammatory response as one of its weapons.”

Researchers report that inhibiting NF-κB in astrocytes had no effect on ALS progression so the search for weapons that astrocytes use against motor neurons still continues. How or why NF-κB causes microglia to turn into neuron-killing agents still remains a mystery, however the current study moves researchers closer to finding therapy for ALS.

Current ALS research is focused in two directions. One path is trying to determine the trigger that leads to ALS onset. The other path is trying to understand the process that leads to ALS progression. It is known that changes in motor neurons leads to ALS onset, however disease progression appears to be determined by alterations to astrocytes, microglia and oligodendrocytes. Most cases of ALS have no family ties to the disease, however some cases are hereditary. Due to the complexity of ALS and the lack of familiar tie, screening before onset is practically impossible.

According to Kaspar, “Focusing on stopping the changes that occur in astrocytes and microglia has clinical relevance because most people don’t know they’re getting ALS. We have identified a pathway in microglia that may be targeted to ultimately slow disease progression in ALS and are exploring potential therapeutic strategies and may have broader implications for diseases such as Alzheimer’s and Parkinson’s Disease amongst others.”

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