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Study in mice yields Angelman advance
Date:2/13/2013

PROVIDENCE, R.I. [Brown University] In a new study in mice, a scientific collaboration centered at Brown University lays out in unprecedented detail a neurological signaling breakdown in Angelman syndrome, a disorder that affects thousands of children each year, characterized by developmental delay, seizures, and other problems. With the new understanding, the team demonstrated how a synthesized, peptide-like compound called CN2097 works to restore neural functions impaired by the disease.

"I think we are really beginning to understand what's going wrong. That's what's very exciting," said John Marshall, professor of medical science in the Department of Molecular Pharmacology, Physiology, and Biotechnology and the senior author of the study in the journal PLOS Biology. However Marshall did caution that it is too early to predict how soon a clinical therapy might arise from the results.

In mice and people, Angelman syndrome arises from flaws in a gene called Ube3A. When it functions properly, the gene limits the amount of a protein called Arc in the brain. Left unchecked by the disease, Arc impairs the development of synapses in the hippocampus. Those neural connections may be essential for proper learning and memory function.

In the new study, Marshall and his colleagues report a series of experiments that show how the abundance of Arc creates such negative effects and how Arc might possibly be defeated and its ill-effects repaired in the lab.

Essentially, Arc interferes with the operation of a synaptic protein called PSD-95, that is required for the actions of a growth factor, known as brain-derived neurotrophic factor (BDNF). This growth factor is released at synaptic contacts and initiates a sequence of molecular interactions necessary for the strengthening of neuronal connections or synapses. In mice with the flawed Ube3A gene, the signals sent by BDNF for memory formation are disrupted.

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

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