Life Extension Update
Friday, October 14, 2011. An article published on October 11, 2011 in the Journal of Neuroscience reveals the discovery of researchers at the University of Pittsburgh School of Medicine and Harvard Medical School of a protective effect for melatonin against disease progression and premature death in a mouse model of Huntington's disease, an inherited disorder that results in involuntary movement, decreased intellectual function and other effects stemming from the loss of neurons in the brain due to a mutant protein. Melatonin is a hormone involved in sleep and immune function which has been found to be reduced in other neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases.
"In earlier work, we screened more than 1,000 FDA-approved drugs to see which ones could block the release of a small protein called cytochrome c from the mitochondria to interrupt a key step in a chain reaction known as apoptosis, or programmed cell death," explained senior investigator Robert M. Friedlander, MD, who is the chair of the Department of Neurological Surgery and UPMC Endowed Professor of neurosurgery and neurobiology. "Melatonin, which we know to be a potent antioxidant, was one of the agents that could do this in the test tube, but we needed to determine if it would also be neuroprotective in a transgenic animal model of Huntington's disease."
In the current research, Dr Friedlander's team injected mice bred to develop Huntington's disease with melatonin or a placebo. Animals that received the hormone experienced a 19 percent delay in the onset of disease, a reduction in disease progression and an 18 percent longer life span compared with the placebo group. When the animals' brain tissue was studied, type 1 melatonin (MT1) receptors were found on the cells' mitochondria. The researchers observed that the receptors were depleted—a finding that was also detected in brain tissue derived from humans afflicted with the disease.
"Extra melatonin might help fill all the available MT1 receptors, allowing the hormone to counter the programmed cell death cascade and thus protect neurons," Dr Friedlander commented. "This suggests that melatonin or similar agents that influence the MT1 receptor have potential as a Huntington's disease treatment, which we've never had before."
"Perhaps the best approach will be to develop a cocktail of drugs that target different molecular pathways that are responsible for creating Huntington's disease," he added. "We plan to see if combining different agents leads to a greater impact on disease progression and mortality."
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