Navigation Links
When nerve meets muscle, biglycan seals the deal
Date:2/14/2012

PROVIDENCE, R.I. [Brown University] A protein that has shown early promise in preventing the loss of muscle function in mouse models of Duchenne muscular dystrophy, has been found in a new study to be a key player in the process of joining nerves to muscles.

The protein biglycan needs to be present to stabilize synapses at the neuromuscular junction after they have formed, according to research led by Brown University that appears in the Feb. 14, 2012, issue of the Journal of Neruoscience.

"What neuromuscular junctions do second-by-second is essential for our brain to control movement and they are also important for the long-term health of both muscle and motor neurons," said Justin Fallon, profesor of neuroscience at Brown University and the paper's senior author. "A treatment that sustains or supports the synapse could promote the health of motor neurons and muscle."

In previous work, Fallon, a member of the Brown Institute for Brain Science, has shown that in mice with the same genetic mutation as Duchenne patients, biglycan promotes the activity of another natural protein, utrophin, that can significantly reduce the muscle degradation that patients suffer. Utrophin essentially takes over for dystrophin, which is the protein Duchenne patients cannot produce. In 2010 Brown licensed Fallon's biglycan intellectual property to the Providence startup company Tivorsan Pharmaceuticals, which is working toward human trials of biglycan.

Last month the Muscular Dystrophy Association, which helped support Fallon's new study, gave Tivorsan a $1 million grant.

Now Fallon's research group has found another important role for biglycan. In the new multi-institutional study, lead author Alison Amenta and a team of other scientists found that biglycan binds and helps activate and target a receptor enzyme called MuSK, which works like a foreman or master regulator over other proteins that build and stabilize the neuromuscular junction.

Mice engineered to lack biglycan developed normal junctions at first, but by five weeks after birth their synapses became much more likely to break into fragmented shadows of their former selves. In experiments the scientists saw that up to 80 percent of synapses in biglycan-lacking mice were unstable.

Biglycan-lacking mice also showed other structural defects including misaligned neurotransmitter receptors and extra folds near synapses.

"We think it is most likely that these folds are remnants of previous synaptic sites," that have since withered, the authors wrote in the paper.

Amenta, Fallon, and their team also found that in mice lacking biglycan, levels of MuSK at neuromuscular junction synapses were reduced by a factor of more than 10. In another experiment, they found that recombinant biglycan could rescue the stability of synaptic structures in model cell culture system.

Relevance to motor neuron diseases

The findings help set the stage for testing biglycan as a potential therapy in animal models of motor neuron disease, Fallon said.

"As an extracellular protein that can be delivered systemically that acts to stabilize the neuromuscular junction, we propose that biglycan could be a protein therapeutic for motor neuron diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis, or ALS," Fallon said.


'/>"/>
Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Source:Eurekalert  

Related biology technology :

1. Department of Defense Awards $5.7 Million Contract to PharmAthene for Nerve Agent Medical Countermeasure Program
2. OSU chemist developing solution to nerve agent exposure
3. Weizmann Institute scientists used accelerated evolution to develop enzymes that provide protection against nerve gas
4. Weizmann Institute scientists used accelerated evolution to develop enzymes that provide protection against nerve gas
5. Biosynthetic corneas formulated with recombinant collagen restore vision and nerve growth
6. New insight in nerve cell communication
7. UCF teams advanced nerve cell system could help cure diabetic neuropathy, related diseases
8. Chimerix Antiviral Compound, CMX001, Meets CMV Phase 2 Primary Endpoint in Allogeneic Hematopoietic Stem Cell Transplant Recipients
9. Nile Therapeutics Announces Top-Line Results in Clinical Trial Evaluating the Subcutaneous Infusion of Cenderitide, Meets Primary Endpoint
10. AllograftPossibilities.org Meets Unmet Need for Consumer-Oriented Information on Tissue Donation, Transplantation on the Internet
11. President Obama Meets U.S. Laureates of 2010 Kavli Prizes
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
When nerve meets muscle, biglycan seals the deal
(Date:5/26/2016)... NY (PRWEB) , ... May 26, 2016 , ... ... decades. FireflySci cuvettes are used in leading laboratories all over the globe. ... day. , In addition to manufacturing awesome cuvettes, FireflySci makes spectrophotometer calibration standards ...
(Date:5/25/2016)... ... May 25, 2016 , ... ... issued by the Office of the National Coordinator for Health IT (ONC) outlining ... if clinically relevant data were available when and where it was needed. The ...
(Date:5/24/2016)... Worcester, Mass. (PRWEB) , ... May 24, 2016 ... ... including heart attacks, diabetes, and traumatic injuries, will be accelerated by research at ... skin cells into engines of wound healing and tissue regeneration. , The novel ...
(Date:5/23/2016)... ... May 23, 2016 , ... ... Precision Farming in 2017 and Beyond. The paper outlines the key trends that ... ag industry. , “We’ve witnessed a lot of highs and lows as the ...
Breaking Biology Technology:
(Date:3/15/2016)... 15, 2016 --> ... Transparency Market Research "Digital Door Lock Systems Market - Global ... 2023," the global digital door lock systems market in terms ... and is forecast to grow at a CAGR of 31.8% ... and medium enterprises (MSMEs) across the world and high industrial ...
(Date:3/11/2016)... 2016 http://www.apimages.com ) - --> ... available at AP Images ( http://www.apimages.com ) - ... to produce the new refugee identity cards. DERMALOG will be unveiling ... in Hanover next week.   --> ... used to produce the new refugee identity cards. DERMALOG will be ...
(Date:3/9/2016)... This BCC Research report provides an overview ... Sequencing (RNA Seq) market for the years 2015, 2016 ... reagents, data analysis, and services. Use this ... market such as RNA-Sequencing tools and reagents, RNA-Sequencing data ... each segment and forecast their market growth, future trends ...
Breaking Biology News(10 mins):