|
||
| |||||||
|
GSK-3 mediates the neurotoxic effects of beta-amyloid Since the mid-1990s, there has been a near exponential rise in the level of glycogen synthase kinase-3 (GSK-3) related research. Consequently, the therapeutic potential of GSK-3 inhibitors has become a major area of pharmaceutical interest. A recent report, produced by LeadDiscoverys' analysts under the editorial guidance of field-leader, Dr Hagit Eldar-Finkelman, offers a state of the art overview of GSK-3 and analyses the therapeutic role that inhibitors of this enzyme may play (Click here for access). The report concludes that there is particularly strong evidence to support the development of GSK-3 inhibitors as 1) antihyperglycemic, insulin sensitizing and insulinotropin agents for use in diabetics; 2) inhibitors of neuronal apoptosis and neurological decline in stroke patients; 3) blockers of the accumulation and toxicity of Aß/tau in Alzheimer's disease (AD). Data implicating GSK-3 in the pathophysiology of AD is particularly strong. GSK-3 is elevated in AD human brain and its activation is able to increase tau phosphorylation and neural cell death, phenomena inhibited by the GSK-3 inhibitors, SB-415286 and SB-216763. Furthermore, GSK-3 inhibition is also able to reduce the release of Aß. This is particularly important since the neurotoxic effect of this protein is generally accepted to play a major role in the neural cell death that accompanies AD progression. More recently, Chilean researchers have reported that Aß-dependent neurotoxicity is related to a loss of function of Wnt signaling components, a well accepted cell survival pathway, and that activation of this signaling cascade prevents such cytotoxic effects. Unlike most protein kinases, GSK-3 is constitutively active in cells and a wide range of extracellular stimuli, including Wnt ligands exert their effects by inhibiting GSK-3 activity. Hence, the neurotoxic effects of inactivating Wnt signaling by Aß may result from uncontrolled GSK-3 activity. This therefore further implicates GSK-3 as a central component of AD pathophysiology and provides additional support for the development of GSK-3 inhibitors as therapeutic options.
November, 2002 Adapted from Inestrosa et al, Neurochem Int 2002 Nov;41(5):341-4 Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk LeadDiscovery 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. |
|
| ||||||||
