PGC-1alpha Versus Huntington’s Disease

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Via ScienceDaily: researchers "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). ... 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. ... [Researchers] 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. 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. ... the mutant form of the htt gene interfered with normal levels and functioning of PGC-1alpha, [and] elevated levels of PGC-1alpha in a mouse model of HD virtually eliminated the problematic misfolded proteins. ... PGC-1alpha influenced expression of another protein vital to autophagy - the process in which healthy cells degrade and recycle old, unneeded or dangerous parts and products, including oxidative, damaging molecules generated by metabolism. For neurons, which must last a lifetime, the self-renewal is essential to survival. ... Mitochondria get beat up and need to be recycled. PGC-1alpha drives this pathway through another protein called transcription factor EB or TFEB. ... If you can induce the bioenergetics and protein quality control pathways of nervous system cells to function properly, by activating the PGC-1alpha pathway and promoting greater TFEB function, you stand a good chance of maintaining neural function for an extended period of time."

Link: http://www.sciencedaily.com/releases/2012/07/120711141853.htm