[tt] Enzymes Key To Brainpower Identified

[Hughes, James J.]

http://www.sciencedaily.com/releases/2007/11/071114200236.htm 	

Enzymes Key To Brainpower Identified

A brain scaffolding protein called PSD-95 could boost cognitive
function. 

ScienceDaily (Nov. 16, 2007) - Bolstering disintegrating neural
connections may help boost brainpower in Alzheimer's disease patients,
MIT researchers and colleagues will report in the Nov. 8 issue of
Neuron.

The researchers zeroed in on the enzymes that manipulate a key
scaffolding protein for synapses, the connections through which brain
cells communicate. Synapses are weakened and lost in neurodegenerative
diseases such as Alzheimer's and Parkinson's disease.

"We identified a major underlying mechanism through which synapses are
strengthened and maintained," said Morgan H. Sheng, Menicon Professor of
Neuroscience at MIT's Picower Institute for Learning and Memory. "The
enzymes involved could be good targets for potential drug treatments."

A protein called postsynaptic density-95 (PSD-95) is a key building
block of synapses. Like the steel girders in a building, it acts as a
scaffold around which other components are assembled. "The more PSD-95
molecules, the bigger and stronger the synapse," said co-author Myung
Jong Kim, a Picower research scientist.

Previous research had shown that mice genetically altered to have less
PSD-95 experienced learning and memory problems.

In the current study, the researchers identified for the first time the
enzymes that work behind the scenes on PSD-95, adding a phosphate group
to a specific amino acid in the PSD-95 protein. This process--called
phosphorylation--is critical for PSD-95 to do its job in supporting
synapses.

"Adding a phosphate group to a single amino acid allows PSD-95 to
promote synapse size and strength," said Sheng, who also holds an
appointment in MIT's Department of Brain and Cognitive Sciences and is a
Howard Hughes Medical Institute investigator. "Therefore, promoting this
process could help improve cognitive function."

Sheng believes manipulating PSD-95 through phosphorylation could lead to
bigger and more robust synapses, which would boost brainpower in both
normal and diseased brains. "It's possible that promoting PSD-95
phosphorylation could also help neuropsychiatric illnesses in which
synapse function goes awry, such as schizophrenia, depression and
autism," Sheng said.

In addition to Sheng and Kim, authors include Picower research scientist
Kensuke Futai; Yasunori Hayashi, MIT assistant professor of neurobiology
and RIKEN-MIT investigator; and Jihoon Yu and Kwangwook Cho of the
University of Bristol in England.

This research is supported by the National Institutes of Health.