Free radical attack on proteins can cause brain stress and loss of nerve cells in dementia
Posted by Scintillon Institute on December 18, 2015
Neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis (ALS), affect approximately 50 million Americans each year, contributing to brain disorders’ significant lead in the global disease burden. This translates into a worldwide cost of $604 billion (roughly 1% of the world’s gross domestic product) for neurodegenerative conditions, including dementia and its related care.
Now, two lead scientists at Scintillon Institute, a rapidly growing non-profit biological research institute focused on fostering the development of tomorrow’s breakthrough technologies, have published a review article on targeting a dysregulated protein in a search for novel therapeutics to solve this international concern.
The article, which was published by the journal Trends in Pharmacological Sciences (CellPress), features groundbreaking work led by Scintillon Institute’s Neurodegenerative Disease Center Professors Tomohiro Nakamura, Ph.D. and Stuart Lipton, M.D., Ph.D and their colleagues.
“This article highlights some of the most exciting recent advances in finding new medicines to fight these diseases,” said Scintillon Institute’s Founding Chair Dr. Jiwu Wang. “Over the years, Drs. Nakamura and Lipton and their colleagues have contributed significantly to our understanding of protein S-nitrosylation and its effects on disease development. This understanding led to the best Alzheimer’s treatment currently on the market, Memantine (brand name Namenda).”
Neurodegenerative diseases result from a gradual and progressive loss of nerve cells and their connections, called synapses, leading to a disabling of the nervous system and resulting in loss of memory and cognitive function. Excessive production of reactive oxygen/nitrogen species, representing free radicals such as nitric oxide (NO), is thought to contribute to this breakdown of nerve cells that occurs in all forms of dementia, of which Alzheimer’s disease is the most common. One in three seniors will die with some form of dementia, according to the Alzheimer’s Association.
Drs. Nakamura and Lipton’s article reviews their current understanding of protein S-nitrosylation, an indiscriminate process whereby free radicals attach themselves to specific sites on proteins, often disrupting their function. Their work sheds light on how to better understand the mechanism to block this reaction on proteins in order to treat dementia and how to optimize the benefits of low concentrations of NO without increasing its destructive qualities. They suggest that correctly timed use of small molecules to prevent aberrant protein S-nitrosylation might be therapeutic. To produce such anti-dementia drugs, they assert that an interdisciplinary approach, in fields as diverse as structural biology, protein biochemistry, and medicinal chemistry, may be needed. Scientists at Scintillon Institute are doing just that!
The work was supported in part by grants from the National Institutes of Health, The Brain and Behavior Research Foundation, and the Michael J. Fox Foundation.
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Scintillon Institute was founded in 2012 as an independent non-profit science research institute with the goal of discovering and developing new biologically based technologies that address the fundamental needs of a growing civilization. Research projects include novel tools for biological imaging, new perspectives on aging and cancer research as well as innovative approaches to developing sustainable energy and food sources. Focused on catalyzing key advances in biological research, it seeks to contribute broadly to improving public health, treating disease, and producing sustainable energy and food for our growing world population.
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