In a paper published in the July 11 online issue of
Science Translational Medicine, researchers at the University of California,
San Diego School of Medicine have identified two key regulatory proteins critical to clearing away misfolded proteins that accumulate and cause the progressive, deadly
neurodegeneration of
Huntington's disease (HD).
The findings explain a fundamental aspect of how HD wreaks havoc within cells and provides "clear, therapeutic opportunities," said principal investigator Albert R. La Spada, MD, PhD, professor of cellular and molecular medicine, chief of the Division of
Genetics in the Department of
Pediatrics and associate director of the Institute for Genomic Medicine at UC San Diego.
"We think the implications are significant," said La Spada. "It's a lead we can vigorously pursue, not just for Huntington's disease, but also for similar neurodegenerative conditions like
Parkinson's disease and maybe even
Alzheimer's disease."
In HD, an inherited mutation in the huntingtin (htt)
gene results in misfolded htt proteins accumulating in certain central
nervous system cells, leading to progressive deterioration of involuntary movement control, cognitive decline and psychological problems. More than 30,000 Americans have HD. There are no effective treatments currently to either cure the disease or slow its progression.
La Spada and colleagues focused on a protein called PGC-1alpha, which helps regulate the creation and operation of mitochondria, the tiny organelles that generate the fuel required for every cell to function.
"
It's all about energy," La Spada said. "Neurons have a constant, high demand for it. They're always on the edge for maintaining adequate levels of energy production. PGC-1alpha regulates the function of transcription factors that promote the creation of mitochondria and allow them to run at full capacity."
