Researchers at privately held Gliatech Inc. have developed atheory that implicates glial nerve cells, which constitute 90percent of the central nervous system (CNS), as playing acausative role in Alzheimer's disease.
This marks a significant departure from current theories, whichcenter on the pivotal role that the beta amyloid protein mayplay in causing the destruction of neurons in Alzheimer's. Thescientists are reporting their experimental data in severalposter sessions throughout this week at the Society ofNeuroscience meeting in Washington, D.C.
Gliatech's research indicates that the beta amyloid proteinwreaks its havoc on the CNS only because it interacts with atype of glial cells known as astrocytes. This interaction inducesthe astrocytes to produce proteoglycans (complexcarbohydrates), which in turn bind up the beta amyloidprotein. And it's that complex, according to Gliatech's theory,that may evolve into the neuritic plaques that arecharacteristic of the disease.
"We know that the neuritic plaques contain beta amyloidbound with proteoglycans," explained Robert Frederickson,Gliatech's chief technology officer. "Those plaques contain dyingneurons, but they are loaded with activated microglia andastrocytes," he said. Moreover, "activated glia are alwaysassociated with senile plaques. Without them, you don't havethe apparent neurotoxic manifestations of the beta amyloidprotein."
Frederickson explained that in petri dishes, cortical neuronsexposed to an immobilized layer of amyloid protein prefer tobind to the amyloid over the substrate in the dish,demonstrating that the beta amyloid protein is not neurotoxicper se.
On the other hand, he continued, cortical astrocytes (glial cells)not only avoid the immobilized amyloid protein, but theyelaborate substances -- specifically proteoglycans -- thatrender the beta amyloid protein unappealing in the future toneurons.
In fact, further research by the Gliatech group hasdemonstrated that these proteoglycans prevent proteases fromdegrading beta amyloid protein (probably the way in which thetroublesome protein is normally eliminated from the brain sothat it doesn't accumulate into plaques).
Frederickson said Gliatech of Cleveland has used rational drugdesign to produce a number of small molecule compounds thatcan reverse the protection afforded to beta amyloid protein bythe proteoglycans.
"We have demonstrated what will prevent the degradation ofthe beta amyloid protein, and we have shown that we canreverse that," Frederickson told BioWorld.
-- Jennifer Van Brunt Senior Editor
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