Can An Existing Blood Pressure Level Drug Atacand Aid Process Alzheimer's Disease
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In laboratory neuronal cultures, an FDA-approved drug used to care for high blood pressure level reduced jail cellular telephone harm frequently linked to Alzheimer's disease, state researchers at Georgetown University Medical Center (GUMC) as well as the National Institutes of Health.
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What is Atacand?
Atacand (Candesartan) belongs to a course of study of drugs called angiotensin receptor blockers (ARBs). It industrial plant past times relaxing blood vessels as well as therefore blood tin menstruum to a greater extent than easily. Candesartan keeps blood vessels from narrowing, which lowers blood pressure level as well as improves blood flow.
Atacand is used to care for high blood pressure level (hypertension).
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Resarechers state their work, published online inwards the journal Alzheimer's Research as well as Therapy, provides data supporting the potential trial of the drug candesartan -- every bit good every bit other Angiotensin receptor blockers (ARBs) for the early on handling of Alzheimer's disease.
"Our findings brand feel inwards many ways." Hypertension reduces blood menstruum throughout the trunk as well as encephalon as well as is a opportunity factor of Alzheimer's disease. Previous epidemiological studies establish that Alzheimer's progression is delayed inwards hypertensive patients treated amongst ARBs," says senior writer Juan M. Saavedra, MD, from GUMC's Department of Pharmacology as well as Physiology.Using neuronal cultures, the researchers explored the activeness of candesartan on the neurotoxic effects of exposure to excessive glutamate, a demonstrated injury factor inwards the early on stages of Alzheimer's disease.
The scientists establish that candesartan prevented glutamate-induced neuronal death. They conducted in-depth factor analyses of the laboratory results, demonstrating that candesartan prevented neuronal inflammation as well as many other pathological processes, including alterations inwards amyloid metabolism, a hallmark of Alzheimer's disease.
"The correlations were impressive -- the seem of 471 genes that were altered past times excess glutamate inwards our cultures were likewise altered inwards encephalon autopsy samples from patients who suffered from Alzheimer's disease. Candesartan normalized seem of these genes inwards our cultures," Elkahloun says."We hypothesize that candesartan, or other members of the ARB group, may non alone irksome progression of Alzheimer's exactly likewise forbid or delay its development," Saavedra says.
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The researchers state this run has immediate translational value, supporting testing candesartan, or other ARBs, inwards controlled clinical studies on patients at early on stages of Alzheimer's disease.
Results
Candesartan prevented glutamate upregulation or downregulation of several hundred genes inwards cultures. Ingenuity pathway analysis as well as factor gear upwardly enrichment analysis revealed that inflammation, cardiovascular illness as well as diabetes cry for transduction pathways as well as amyloid β metabolism were major components of the neuronal answer to glutamate excitotoxicity.
Further analysis showed associations of glutamate-induced changes inwards the seem of several hundred genes, normalized past times candesartan, amongst similar alterations observed inwards hippocampus from Alzheimer’s illness patients. Gene analysis of neurons as well as cerebrovascular endothelial cells obtained past times Light Amplification by Stimulated Emission of Radiation capture microdissection revealed that genes up- as well as downregulated past times glutamate were preferentially expressed inwards endothelial cells as well as neurons, respectively.
Conclusions
Data may hold upwardly interpreted every bit evidence of straight candesartan neuroprotection beyond its effects on blood pressure, revealing mutual as well as novel illness mechanisms that may underlie the inwards vitro factor alterations reported hither as well as glutamate-induced jail cellular telephone injury inwards Alzheimer’s disease.
Observations render novel evidence for candesartan neuroprotection through early on molecular mechanisms of injury inwards Alzheimer’s disease, supporting testing this chemical compound inwards controlled clinical studies inwards the early on stages of the illness.
Citation
An integrative genome-wide transcriptome reveals that candesartan is neuroprotective as well as a candidate therapeutic for Alzheimer’s disease
DOI: 10.1186/s13195-015-0167-5
http://bit.ly/1SrNDsb
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The run was supported past times grants from the National Institutes of Health including the National Human Genome Research Institute (MD 20892) as well as the National Institute of Mental Health (MH 002762-16). The authors study having no personal fiscal interests related to the study.
About Georgetown University Medical Center
Georgetown University Medical Center is an internationally recognized academic medical centre amongst a three-part mission of research, pedagogy as well as patient assist (through MedStar Health).
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