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Specific inhibitors of Aß42 accumulation Approximately 15 percent of people who live to the age of 65 will develop some form of dementia; by age 85, that proportion increases to at least 35 percent. The most common of all the dementias is Alzheimer's disease. Four million Americans currently suffer from the condition, and experts estimate that 22 million people around the world will be so afflicted by 2025. Aß42 is invariably elevated with all mutations that cause the less common familial Alzheimer's disease and is also generally considered to be of key importance to the development of late onset disease. This form of ß-amyloid forms toxic fibrils much faster than Aß40, its shorter homologue and strategies for specifically reducing Aß42 accumulation are actively being sought (Click here for access to our recent dossier "CBE-2001, a therapeutic candidate for Alzheimer's disease identified using AMYScreen an HTS screen for specific inhibitors of Aß42 accumulation"). Epidemiological studies have documented a reduced prevalence of Alzheimer's disease among users of NSAIDs; UCSD researchers now reports that the NSAIDs ibuprofen, indomethacin and sulindac sulphide preferentially decrease Aß42 produced from a variety of cultured cells by as much as 80%. This effect was not seen in all NSAIDs and seems not to be mediated by inhibition of cyclooxygenase activity, the principal pharmacological target of NSAIDs. Furthermore, short-term administration of ibuprofen to mice that produce mutant beta-amyloid precursor protein (APP) lowered their brain levels of Aß42. In cultured cells, the decrease in Aß42 secretion was accompanied by an increase in the Aß(1-38) isoform, indicating that NSAIDs subtly alter gamma-secretase activity without significantly perturbing other APP processing pathways or Notch cleavage. This highly exciting data suggests that libraries of NSAIDs should be screened for similar activity and SAR studies performed to identify candidate pharmacophores for further optimization. Projects such as these are overviewed in full DiscoveryDossiers. DiscoveryDossiers ~ TherapeuticsAdvances ~ PharmaceuticalSolutions ~ LeadDiscovery ~ Purchase DiscoveryDossiersLeadDiscovery and BioPortfolio aims to provide reliable, insightful analysis on the biotechnology industry. However, this information is provided "as is" and no representations or warranties either express or implied of completeness, accuracy, or of any other nature are made with respect to this information. This information is neither an offer to sell nor a solicitation to buy the securities of any company. This information contains forward-looking statements, which involve risks and uncertainties which may not be listed. The biotechnology industry is an emerging industry and the securities of the companies mentioned in this report have a very high degree of risk and volatility. For this reason, this information is supplied on the condition that the reader will make his or her own determination as to its suitability for any purpose prior to any use of this information. The employees and officers of LeadDiscovery and BioPortfolio may hold positions in some or all of the stocks discussed in this report. This abstract has been produced by LeadDiscovery Ltd. Founded by life scientists for life scientists we aim to help industry identify cutting edge drug discovery options and academic/biotech institutions maximize the potential of their research. Abstracts strictly reflect the opinion of LeadDiscovery's editorial panel. While all reasonable efforts are made to ensure the accuracy of information provided LeadDiscovery and the publisher BioPortfolio, takes no responsibility for incorrect or misleading information. LeadDiscovery is designed for educational and drug development purposes only and is not intended or designed to offer medical advice or advice of any sort, and must not be used for such purpose. The information provided through LeadDiscovery and BioPortfolio should not be used for diagnosing or treating a health problem or a disease and no reliance should be placed on any information contained in this abstract or elsewhere on LeadDiscovery's and BioPortfolio's website. It is not intended to be a substitute for professional care. If you have or suspect you may have a health problem, you should consult your physician or other health care provider. |
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