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Virginia Tech Engineer Investigates Enzyme Link To Neurological Disease

Date:
September 3, 2005
Source:
Virginia Tech
Summary:
Two Virginia Tech engineers are evaluating specific therapies to fight abnormally high protein binding that can cause neurological disorders.
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Several neurologically based afflictions, such as Huntington's,Parkinson's, and Alzheimer diseases, have been correlated to a higherthan normal presence of a specific type of enzymes, calledtransglutaminases (TGase) in the human body. TGases, whose function isto catalyze covalent bonds among proteins, are commonly found inseveral different human tissues.

In the presence of unusually high levels of these enzymes, someproteins tend to form denser clusters than normal in vivo. If theaggregates grow in size, it can lead to a build-up of insoluble plaquesthat can block neurovascular transport and cause neural cell death.

"If higher TGase concentrations in cerebrospinal fluid and in the brainlead to protein agglomeration, then their inhibition could reducesymptoms, delay the onset of agglomeration, and maintain viable neuralcell health extending the quality of life for those afflicted,"hypothesizes Brian Love, a professor of materials science andengineering (MSE) at Virginia Tech.

Love, who focuses his research on tissue and cell engineering,and Elena Fernandez Burguera, a post-doctoral research associate, areevaluating specific therapies to fight the abnormally high TGasebinding. Based upon the prior work of several others who are conductingclinical trials, Love and Burguera are developing an in vitro model toevaluate the ability of several inhibitors to block protein aggregationby TGases.

Again, based on the work of other scientists, "several compounds showsome positive effects," Love says. These include creatine, cystaminehydrochloride, and a few others. "The development of an inhibitionprotocol may help test the efficacy of other inhibitors as well," theengineer adds.

The Virginia Tech researchers are looking at the enzymatic binding ofprotein-bound polystyrene particles as models. Groups of particles aredispersed in calcium-rich aqueous solutions containing TGases. Oncemixed, the particle binding begins. The bigger agglomerates attempt tosettle out of the solution, and Love and Burguera track particlesedimentation.

The tracking method, called Z-axis Translating Laser Light Scattering(ZATLLS), is unique to Virginia Tech and based on key concepts intransport phenomena. It has been used to gauge how other complexfluids, such as paints and sealants, are dispersed. Now Love andBurguera are resolving when protein coated particles are effectivelydispersed in vitro and under what conditions they are unstable enoughto agglomerate.

They track in situ sedimentation of protein-coated particles exposed totransglutaminase, both in the presence of and without transglutaminaseinhibitors. "We can use ZATLLS to resolve whether inhibitors preventagglomeration of protein coated particles by TGase if the inhibitorslower the particle sedimentation velocity," Love says. "Our goal is tofind the safest and most effective inhibitors that prevent theagglomeration-based crosslinking found throughout these neurologicaldisorders."

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This work is funded by the Commonwealth Health Research Board.

Love is a participating member in the School of Biomedical Engineeringand Science (SBES), a joint venture between Virginia Tech's College ofEngineering and the Wake Forest University School of Medicine. SBES isthe partnership of the two eminent educational institutions.


Story Source:

Materials provided by Virginia Tech. Note: Content may be edited for style and length.


Cite This Page:

Virginia Tech. "Virginia Tech Engineer Investigates Enzyme Link To Neurological Disease." ScienceDaily. ScienceDaily, 3 September 2005. <www.sciencedaily.com/releases/2005/08/050831075406.htm>.
Virginia Tech. (2005, September 3). Virginia Tech Engineer Investigates Enzyme Link To Neurological Disease. ScienceDaily. Retrieved June 18, 2024 from www.sciencedaily.com/releases/2005/08/050831075406.htm
Virginia Tech. "Virginia Tech Engineer Investigates Enzyme Link To Neurological Disease." ScienceDaily. www.sciencedaily.com/releases/2005/08/050831075406.htm (accessed June 18, 2024).

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