UCSF study points to link to neurodegenerative disease target

September 01, 2005

A UCSF study has found that a specific signaling link between neurons and muscles in the fruit fly is essential for keeping the insect's nervous system stable.

The findings are relevant for ongoing research in identifying causes and developing treatments for neuromuscular neurodegenerative diseases in humans, such as amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, says study co-author Graeme Davis, PhD, associate professor and vice chair of the Department of Biochemistry and Biophysics at the University of California, San Francisco.

"If we want to make new drugs to treat neurodegenerative disease, then we have to identify new drug targets, and our study findings present that potential," he says. "This study is a significant step forward because we have shown that a signaling system composed of several genes is important for keeping the nervous system stable."

The findings are reported in the September issue of the journal Neuron.

The nervous system is a complex pattern of connections that exists for the entire life of the organism, and understanding how the myriad patterns and pathways of these connections are maintained for long periods of time presents an ongoing challenge to scientists, says Davis.

Davis and co-author Benjamin Eaton, PhD, a post-doctoral fellow in Davis' lab, were led to the new discovery through ongoing experiments with a signaling system in fruit flies that is tied to a protein called bone morphogenetic protein, or BMP. They found that the BMP signaling system is required for the long-term stability of the neuromuscular synapse, the point where a nervous impulse passes from a neuron to a muscle to cause muscle movement.

In the absence of BMP signaling, their research showed, the synapse between the nerve and muscle disassembles and degenerates. This observation enabled the team to look for new genes involved in the BMP signaling system, which led to the identification of specific stabilizing factors in the nervous system.

"It is a very complicated task to keep the nervous system stable. We are using a model organism, the fruit fly, to help us rapidly identify the genetic basis for the long-term stability," Davis says. "What we have been able to do with this study is to hone in on several genes that are essential for this stability."

By examining genetic mutations that delete individual genes, the scientists were able to demonstrate that BMP signaling is required for the stability of synaptic connections. Further genetic tests demonstrated that a cytoplasmic enzyme called LIM Kinase1 is an essential link that enables BMP signaling molecules to stabilize the synapse.

Davis notes that working with fruit flies allows scientists to identify the function of new genes very rapidly. "We can easily observe the connections between the nerve and muscle, and see if the nerve is degenerating. Each week we can test hundreds of genes and determine if they are important for stabilizing the synapse between the nerve and muscle."

"The signaling molecules that are present in fruit flies are basically the same as in humans," explains Davis. "In a matter of a few years we hope to test the function of every gene in the genome and identify a whole array of genes that are necessary to keep the neuromuscular synapse stable."

ALS, for example, is a degenerative neuromuscular disease. "If we can find a way to keep the neuromuscular synapse stable, then we might be able to slow down the rate of degeneration," he adds.

"With ALS and other neuromuscular degenerative diseases, only a handful of genes have been identified that either cause the diseases or contribute to their progression."

"The exciting thing about this study," says Davis, "is that it starts to tell us how we can keep a synapse stable. And that can lead us to understanding why synapses degenerate at the muscle cells of people with ALS. If we can identify more genes that are important for synapse stability, then there will be more targets for the development of new drugs to treat these diseases. Currently, the number of potential targets for new drug development is quite limiting and we hope to help change that. This is an exciting time with the potential for real progress in terms of understanding the biology of these diseases."

University of California - San Francisco

Related Nervous System Articles from Brightsurf:

Chikungunya may affect central nervous system as well as joints and lungs
Investigation conducted by international group of researchers showed that chikungunya virus can cause neurological infections.

Glial cells play an active role in the nervous system
Researchers at M√ľnster University, Germany, have discovered that glial cells - one of the main components of the brain -not only control the speed of nerve conduction, but also influence the precision of signal transduction in the brain.

Protein produced by the nervous system may help treatments for inflammatory diseases
A Rutgers-led team discover a protein produced by nervous system may be key to treating inflammatory diseases like asthma, allergies, chronic fibrosis and chronic obstructive pulmonary disease (COPD)

COVID-19 may attack patients' central nervous system
''There may be more central nervous system penetration of the virus than we think based on the prevalence of olfaction-associated depressed mood and anxiety and this really opens up doors for future investigations to look at how the virus may interact with the central nervous system,'' explains Ahmad Sedaghat, MD, PhD.

Lifting weights makes your nervous system stronger, too
Gym-goers may get frustrated when they don't see results from weightlifting right away, but their efforts are not in vain: the first few weeks of training strengthen the nervous system, not muscles.

COVID-19 threatens the entire nervous system
A new review of neurological symptoms of COVID-19 patients in current scientific literature reveals the disease poses a global threat to the entire nervous system.

Fewer scars in the central nervous system
Researchers have discovered the influence of the coagulation factor fibrinogen on the damaged brain.

Polymerized estrogen shown to protect nervous system cells
In research published today in Nature Communications, an interdisciplinary team from Rensselaer Polytechnic Institute demonstrated how estrogen -- a natural hormone produced in the body -- can be polymerized into a slow-releasing biomaterial and applied to nervous system cells to protect those cells and even promote regeneration.

Discovery concerning the nervous system overturns a previous theory
It appears that when our nervous system is developing, only the most viable neurons survive, while immature neurons are weeded out and die.

Autonomic nervous system appears to function well regardless of mode of childbirth
'In a low-risk group of babies born full-term, the autonomic nervous system and cortical systems appear to function well regardless of whether infants were exposed to labor prior to birth,' says Sarah B.

Read More: Nervous System News and Nervous System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.