Newly Discovered Enzyme Pathway to Nerve Cell Death May Lead to New Therapies for Neurological Diseases
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NR-02-05 (sent 8/8/02). For more information, please call Joe Carey at 202-745-5138 or Nancy Beddingfield at 858-646-3146.
NEWLY DISCOVERED ENZYME PATHWAY TO NERVE CELL DEATH MAY LEAD TO NEW THERAPIES FOR NEUROLOGICAL DISEASES
WASHINGTON, DC August 8 - Nitric oxide, a gas found in the body and as an air pollutant, can activate enzymes outside nerve cells to trigger their demise during stroke and neurodegenerative diseases, such as Alzheimer's disease, multiple sclerosis and AIDS dementia, says a new study.
The enzymes belong to a family known as matrix metalloproteinases or MMPs. When activated in excess, these enzymes chew up the outside of nerve cells, resulting in their death. The new study, funded primarily by the National Institutes of Health, appears in the August 16, 2002 issue of Science magazine.
"Now that we know about this new pathway to nerve cell death that occurs outside of the cells, we can design drugs to interrupt it," says Stuart A. Lipton, MD, PhD, a neurologist at The Burnham Institute in La Jolla, CA and head of the research team. Lipton and his colleagues are starting to test such drugs in rodent stroke models.
Multiple molecular pathways contribute to brain damage in patients with stroke. Two of these are the gaseous neurotransmitter nitric oxide (NO) who's release in excess leads to stroke damage, and MMPs which are activated by strokes and cause tissue damage. "Lipton and colleagues have now linked the two, clarifying how strokes are generated and suggesting novel therapies," says Solomon Snyder, MD, a neuroscientist at Johns Hopkins Medical School. "The new discoveries suggest that targeting nitric oxide and MMP together might have synergistic effects amplifying anti-stroke effects."
Using mass spectrometry, a method that allows precise characterization of proteins, including enzymes, Lipton and his colleagues found that the MMP enzymes are not only activated by NO, but also that the MMPs are further affected by oxygen-related molecules to produce permanent and pathological activity of the enzymes, leading them to chew up the normal environment surrounding the nerve cell. This heightened activity occurs predominantly during periods of stress or disease, and results in the death of the nerve cells by a process known as apoptosis.
Lipton's co-authors include Zezong Gu, Marcus Kaul, Boxu Yan, Steven J. Kridel, Jiankun Cui, Alex Strongin, Jeffrey W. Smith and Robert C. Liddington. Lipton is a member of the Society for Neuroscience, an organization of more than 29,000 basic scientists and clinicians who study the brain and nervous system. He can be reached through Nancy Beddingfield at The Burnham Institute at 858-646-3146.