When ground squirrels hibernate, they dramatically reduce the flow of blood to their brains. Yet the squirrels suffer no ill effects, thanks to a cellular process called SUMOylation. By burrowing into the SUMOylation secrets hoarded by squirrels, scientists hope to retrieve molecular boons for people who suffer ischemic stroke, which typically results from a blood clot, constrains blood flow to part of the brain, and deprives brain cells of oxygen and nutrients.
SUMOylation refers to a kind of protein modification that regulates protein function in various cellular processes. In hibernating ground squirrels, SUMOylation is heightened—a hint that SUMOylation tags, small ubiquitin-like modifiers (SUMOs), may protect brain cells when oxygen and glucose become scarce.
By identifying molecules that can target the SUMO system, scientists based at the NIH have identified a potential drug that could allow stroke patients to emulate the cellular changes that protect hibernating animals. The drug, like proteins found in the hibernating ground squirrel, inhibits molecular processes that diminish SUMOylation.
The potential drug was evaluated in an article (“Quantitative High-Throughput Screening Identifies Cytoprotective Molecules That Enhance SUMO Conjugation via the Inhibition of SUMO-Specific Protease (SENP)2”) that appeared November 16 in The FASEB Journal. According to this article, post-translational modifications such as SUMOylation have emerged as critical molecular regulatory mechanisms in states of both homeostasis and ischemic stress.
“For decades scientists have been searching for an effective brain-protecting stroke therapy to no avail,” said Francesca Bosetti, Ph.D., Pharm.D., program director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS). “If the compound identified in this study successfully reduces tissue death and improves recovery in further experiments, it could lead to new approaches for preserving brain cells after an ischemic stroke.”
At present, the only way to minimize stroke-induced cell death is to remove the clot as soon as possible. A treatment to help brain cells survive a stroke-induced lack of oxygen and glucose could dramatically improve patient outcomes, but no such neuroprotective agents for stroke patients exist.
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