New compounds may help develop drugs for degenerative nerve diseases

January 20th, 2010 - 3:14 pm ICT by ANI  

Washington, Jan 20 (ANI): Scientists at Duke University Medical Centre have discovered certain compounds that could lead to promising new drugs for degenerative nerve diseases, such as Huntington’s disease, Alzheimer’s disease and Parkinson’s disease.

Misfolded proteins in nerve cells (neurons) are a common factor in all of these diseases.

These new compounds improve a cell’s ability to properly “fold” proteins.

It activates a master regulator to increase the supply of “protein chaperone” molecules that help fold proteins properly.

The scientists further explored one of the candidate molecules to activate the master regulator of chaperone gene expression, Heat Shock Factor 1 (HSF1), to learn whether it would work in model systems of Huntington’s disease, a devastating neurodegenerative disease of protein misfolding.

They were able to show that the molecule stimulated protein chaperones in cells and in an animal system.

The damage to early-state rat neurons was much lower in cells pre-treated with the HSF1 activator, and damage to the neurons of fruit flies that had a Huntington’s-like disorder was also greatly reduced.

The study provides a new approach to address the root cause of these diseases - protein misfolding.

“The advantage of our screen is that it identifies molecules that can elevate the levels of chaperones without inducing cellular stress and that don’t inhibit a key protein chaperone called Hsp90 that is needed for cells to function normally,” said senior author Dennis J. Thiele, Ph.D., Professor of Pharmacology and Cancer Biology.

“We found a creative way to identify new molecules that can activate the body’s natural protein folding machinery,” he added.

Lead author Daniel Neef, Ph.D., says they used genetically altered yeast to find compounds that might aid chaperone development.

The study appears online in PLoS Biology. (ANI)

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