Metallo-complex activation of neuroprotective signalling pathways as a therapeutic treatment for Alzheimer's disease.
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| Abstract |
Alzheimer's disease is the most common neurodegenerative disease of the elderly and although some drugs may delay cognitive impairment, an effective treatment has not yet been found. Extracellular deposition of amyloid-beta (Abeta) plaques, intracellular hyperphosphorylation of the microtubule associated protein, tau and elevated oxidative stress have long been a focus for neurotherapeutic strategies. More recently biometal interactions with Abeta have become a feasible target as they appear to play a significant role in the pathogenesis of this devastating disease. Metal ligands such as 8-hydroxyquinoline derivatives have been developed that alter these interactions and promote clearance of amyloid deposits. A novel neurotherapeutic approach may involve activation of neuronal cell signalling mechanisms using metallo-complexes. Copper or zinc complexes can activate phosphoinositol-3-kinase leading to downstream modulation of glycogen synthase kinase-3 and extracellular signal regulated kinase and this results in decreased tau and Abeta levels. These approaches may offer a new strategy for treating AD. Further in vivo investigation is required to elucidate the mechanism of action of these metallo-complexes in vivo and determine their efficacy and safety as potential treatments of neurodegenerative diseases.
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| Authors | Laura Bica, Peter J Crouch, Roberto Cappai, Anthony R White |
| Journal | Molecular bioSystems (Mol Biosyst) Vol. 5 Issue 2 Pg. 134-42 (Feb 2009) ISSN: 1742-2051 [Electronic] England |
| PMID | 19156258 (Publication Type: Journal Article, Review) |
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