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Do squirrels hibernate in massachusetts8/11/2023 Remarkably, ebselen also increased SUMOylation levels in the brains of fully-grown mice.įollowing the success of their study, the researchers now aim to investigate if boosting SUMOylation levels with ebselen can actually protect the brains of animal models during stroke-like conditions. Four compounds: ebselen, 6-thioguanine, isoprenaline hydrochloride and ethyl protocatechuate increased SUMOylation levels.įurther testing showed that two of the compounds, ebselen and 6-thioguanine, not only increased SUMOylation levels in rat neuronal cells but also protected the cells when they were deprived of oxygen and glucose in vitro. These eight compounds were then co-cultured with rat neuronal cells to assess whether they could boost SUMOylation levels. Eventually, after a lengthy screening process, eight compounds were identified as potential inhibitors of SENP2 activity. The research team used CETSA to evaluate how well each small molecule compound engaged with the SENP2 protein. Bernstock and Hallenbeck utilized to narrow down the over 4,000 candidate compounds was cellular thermal shift assay (CETSA). Essentially, by blocking SENP2, the researchers hoped to suppress an inhibitor of SUMOylation and thereby increase global SUMOylation levels. Compounds that inhibit an anti-SUMOylation protein called SUMO-specific isopeptidase (SENP2) were targeted. They examined 4,096 small molecules to identify compounds that could boost SUMOylation. In doing so, they hoped to ultimately develop a compound that could be used in clinical settings. By artificially increasing SUMOylation levels using small molecule drugs, the researchers hoped to emulate the 13-lined ground squirrel and achieve greater resilience against reduced blood flow. Bernstock and Hallenbeck investigated whether classes of small molecules could be identified that could artificially increase SUMOylation levels in pertinent murine models. While the team has pursued a variety of modalities in an effort to therapeutically engage SUMOylation, a recent study by Drs. “These squirrels are having bouts of ischemia (decreased blood flow) - in the context of hibernation - that are more extreme than any human stroke, yet have no cellular pathology, no behavioral deficits,” explained Dr. Hallenbeck to study the ischemic tolerance of the 13-lined ground squirrel. Bernstock, a neurosurgeon-scientist, collaborated with Dr. Hallenbeck observed that SUMOylation dramatically increased in 13-lined ground squirrels during hibernation and this allowed the squirrels to endure extreme conditions while hibernating.ĭr. During SUMOylation, Small Ubiquitin-like Modifier (SUMO) proteins bind to other proteins and in so doing modify their activity, location, and/or stress responses. He and his team discovered the ischemic resilience of the 13-lined ground squirrel is driven in large part by a post-translational cellular process called SUMOylation. He was a pioneer in squirrel-stroke research. Hallenbeck is an emeritus senior investigator at the National Institutes of Health (NIH) and the former director of the Stroke Branch at the National Institute of Neurological Disorders and Stroke (NINDS). Reduced blood flow during ischemic stroke cuts off much-needed oxygen and glucose (a type of sugar), resulting in neuronal/glial cell death.ĭr. These strokes occur when blood vessels in the brain become obstructed. Globally, over 7.6 million people suffer from ischemic strokes each year. Juxtaposed with the resilience of the 13-lined ground squirrel brain is the fragility of the human brain. In fact, it ranks among the “most brain hypoperfusion-tolerant mammals known,” boasting remarkable tolerance to reduced blood flow to the brain. Yet, despite the relative lack of oxygen and nutrients caused by reduced cerebral blood flow, the 13-lined ground squirrel survives. The squirrel’s heart rate, metabolism, and body temperature decrease considerably, slowing down blood flow to its brain. The 13-lined ground squirrel hibernates every winter, passing into a deep, dormant state to avoid the harsh freezing climate. Yet, underneath the prairie soil, sleeping peacefully in its cozy winter burrow is the 13-lined ground squirrel (aka Ictidomys tridecemlineatus). WHOOSH! A powerful wind sweeps across the prairie, engulfing all flora and fauna lying in its path.
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