A Promising New Approach for Treating Alzheimer’s Discovered
Researchers at the Disease Center at Columbia University Medical Center in New York have discovered a new class of compounds, called "pharmacologic chaperones," which could pave the way to Alzheimer's treatment in near future.
The researchers used computer-based virtual screening to identify the new "chaperone" compounds. They say these compounds can greatly increase retromer levels and decrease amyloid-beta levels in hippocampal neurons. A so-called retromer protein complex has a pivotal role in neurons by steering away amyloid precursor protein (APP) from a part of the cell where it is split, creating amyloid-beta - a potentially toxic byproduct regarded as a hallmark of Alzheimer's.
According to Dr. Scott Small, director of the Alzheimer's Disease Center at Columbia University Medical Center in New York and lead researcher, the findings identify a novel class of pharmacologic agents that are designed to treat neurologic disease by targeting a defect in cell biology, rather than a defect in molecular biology. He added that their approach may prove safer and more effective than the treatments that are being used for neurologic disease, which typically target single proteins.
The team screened known chemical compounds using virtual simulations, to find the association between compounds and the retromer protein complex. 100 potential candidates that could stabilize retromer were identified, 24 of them showed promise. R55, in particular increased retromer's stability, even when it was subjected to a heat stress test. Now, the team is testing the compound's clinical effects in mouse models. Thereafter, they assessed how R55 affected neurons in the brain region involved in learning and memory (hippocampus). There was a concern that these compounds would be toxic, but investigation found it to be "relatively non-toxic.
Earlier, they had found that in the brains of patients with Alzheimer's disease, retromer is deficient. Following it up, they have demonstrated how reducing retromer levels in cultured neurons raised amyloid-beta levels, and vice versa.
The study was published in the Nature Chemical Biology journal.
(Source:Medical News Today)
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Source: Onlymyhealth editorial team Apr 23, 2014
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