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Mol. BioSyst., 2009, 5, 134 - 142, DOI: 10.1039/b816577g
Metallo-complex activation of neuroprotective signalling pathways as a therapeutic treatment for Alzheimer
s diseaseLaura Bica, Peter J. Crouch, Roberto Cappai and Anthony R. White
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 (A
) 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 A 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 A 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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