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Four million
Americans currently suffer from Alzheimer's disease (AD), and experts estimate
that 22 million people around the world will be so afflicted by 2025.
Acetylcholinestase inhibitors dominate the current AD market driving value of
this therapeutic class to over US$1.2 billion in 2001. Although current AD
treatments center on treating symptoms, future strategies are more likely to
modify the course of the disease. The most widely accepted hypothesis on the
etiopathogenesis of AD proposes that aggregates of the Abeta form in the
brain. Under normal conditions, the predominant amyloid peptide secreted is
Abeta(1-40) with about 10-15% being the longer 1-42 form. In AD there appears
to be an increase in the longer more toxic form which is proposed to trigger
tau hyperphosphorylation and neural degeneration. Neurotoxicity is thought to
be due to altered calcium regulation, mitochondrial damage and/or immune
stimulation. One strategy for treating AD is the prevention of Abeta release
or the blockade of it neurotoxic activity. As discussed in
our recent DiscoveryDossier, the use of glycogen synthase kinase (GSK)-3
inhibitors is rapidly emerging as a highly promising small molecule approach
to AD as well as a host of other serious conditions (click
here for dossier access). GSK-3 is elevated in AD brain, phosphorylating
tau and also possibly providing a common docking site for tau and
presenelin-1, a further protein associated with AD. GSK-3 inhibitors prevent
tau hyperphosphorylation, reduce the release of Abeta from transfected COS7
cells and also protect cultured neurons from cell death triggered by Abeta. A further strategy is to identify therapeutics able to remove beta amyloid and treatments that can focus on Abeta(1-42) would hold a particular advantage.In this respect recent data published by Jens Husemann and colleagues in this month’s Nature medicine are particularly interesting. This group has investigated the characteristic accumulation of astrocytes at sites of Abeta deposition early on in the course of AD. In particular they show that cultured adult mouse astrocytes migrate in response to monocyte chemoattractant protein-1 (MCP-1), a chemokine present in AD lesions, and cease migration upon interaction with immobilized Abeta(1-42). The ability of astrocytes to bind and degrade Abeta(1-42) was also reported. Astrocytes plated on Abeta-laden brain sections from a mouse model of AD associate with the Abeta deposits and reduce overall Abeta levels in these sections. These results suggest a novel mechanism for the accumulation of astrocytes around Abeta deposits and indicate a direct role for astrocytes in degradation of Abeta. Treatments that increase removal of Abeta by astrocytes may therefore be a critical mechanism to reduce the neurodegeneration associated with AD. Entry date Adapted from Wyss-Coray et al, Nat Med 2003 Apr;9(4):453-7 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.
Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk Projects such as these are overviewed in full DiscoveryDossiers. 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. |
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