Lysosome Impairment Can Cause Excess Iron Found in Brains of Those with Parkinson’s Disease; Normally Sequestered Iron Escapes into Body of Neuron Where It Causes Toxic Oxidative Stress Leading to Neuronal Cell Death

It's long been known that excess iron is found in the brains of patients with Parkinson's disease, an incurable neurodegenerative condition that affects motor function. The mechanism by which the iron wreaks damage on neurons involved in Parkinson's disease has not been clear. Now, new research from the laboratory of Julie K. Andersen, Ph.D, at the Buck Institute for Research on Aging in Novato, California just north of San Francisco, suggests that the damage stems from an impairment in the lysosome, the organelle that acts as a cellular recycling center for damaged proteins. Dr. Andersen and collaborators report that the lysosome impairment allows excess iron to escape into the neurons where it causes toxic oxidative stress. The research was published online in The Journal of Neuroscience on January 27, 2016. The article is titled “Regulation of ATP13A2 via PHD2-HIF1 Signaling Is Critical for Cellular Iron Homeostasis: Implications for Parkinson's Disease.” Lysosomes are key to a process called autophagy, whereby damaged proteins are broken down into building blocks that are used to make newly-built proteins to take their place. It's the cellular equivalent of recycling. With age, the ability of the lysosome to participate in autophagy becomes slower, resulting in the build-up of non-protein "garbage" within the cells. Less-than-optimal autophagy has been associated with several age-related diseases, including Parkinson’s disease. "It's recently been realized that one of the most important functions of the lysosome is to store iron in a place in the cell where it is not accessible to participate in toxic oxidative stress-producing reactions," said Dr. Andersen, Senior Scientist and faculty member at the Buck Institute.
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