Scientists at the University of Kentucky College of Medicine have determined how an enzyme essential for energy metabolism functions, solving a mystery eluding molecular biologists for decades.
Matthew Gentry, Ph.D, and Craig Vander Kooi, Ph.D, associate professors of molecular and cellular biochemistry, and researcher Madushi Raththagala, Ph.D, recently discovered the role of the enzyme laforin in modifying human glycogen and thereby preventing neurodegeneration.
Their work provides fundamental insights that link energy metabolism with the fatal, neurodegenerative form of epilepsy called Lafora disease. These findings were reported Jan. 22, 2015, in the journal, Molecular Cell.
Lafora disease was first described by Gonzalo Rodriquez-Lafora in 1911. In 1998, a team of scientists at University of Toronto identified the laforin gene as being mutated in Lafora disease patients. Mutations in the gene encoding the laforin protein result in the accumulation aberrant glycogen-like accumulations called Lafora bodies that resemble plant starch more than human glycogen.
Previous research showed Lafora bodies are the driving agents of Lafora disease. Lafora disease patients develop normally until their second decade of life when they experience an epileptic episode. These episodes increase in severity and number until the patient eventually dies from a massive seizure, status epilepticus or aspiration pneumonia.
Through their research, Raththagala, Vander Kooi, and Gentry determined the structural basis for the specific enzymatic function of laforin. This discovery allowed them to define how laforin modifies glycogen to inhibit Lafora body formation. Additionally, their work defines why specific patient mutations in laforin result in the disease, which opens pathways to understanding and treating the disease.
“A number of groups have tried to determine the structure of laforin over the last 17 years and no one had succeeded,” Gentry said. “Dr. Raththagala worked tirelessly trying different strategies that we developed to achieve this goal. When we realized our success to get over the final hurdle, I had to sit down to fully comprehend our accomplishment. It is exciting to report this structure, but even more exciting to now consider potential therapeutic possibilities.”
MEDIA CONTACT: Elizabeth Adams, email@example.com
Elizabeth Adams | newswise
New flexible, transparent, wearable biopatch, improves cellular observation, drug delivery
12.11.2018 | Purdue University
Exosomes 'swarm' to protect against bacteria inhaled through the nose
12.11.2018 | Massachusetts Eye and Ear Infirmary
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly
The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...
Scientists developed specially coated nanometer-sized vehicles that can be actively moved through dense tissue like the vitreous of the eye. So far, the transport of nano-vehicles has only been demonstrated in model systems or biological fluids, but not in real tissue. The work was published in the journal Science Advances and constitutes one step further towards nanorobots becoming minimally-invasive tools for precisely delivering medicine to where it is needed.
Researchers of the “Micro, Nano and Molecular Systems” Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, together with an international...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
12.11.2018 | Life Sciences
12.11.2018 | Materials Sciences
12.11.2018 | Physics and Astronomy