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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Chemical References |
- Amyloid beta-Peptides
- Ligands
- Metals
- Neuroprotective Agents
- tau Proteins
- Oxyquinoline
- Extracellular Signal-Regulated MAP Kinases
- Glycogen Synthase Kinase 3
- Zinc
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Topics |
- Alzheimer Disease
(metabolism, therapy)
- Amyloid beta-Peptides
(metabolism)
- Animals
- Extracellular Signal-Regulated MAP Kinases
(metabolism)
- Glycogen Synthase Kinase 3
(metabolism)
- Humans
- Ligands
- Metals
(chemistry)
- Neuroprotective Agents
(pharmacology)
- Oxidative Stress
- Oxyquinoline
(pharmacology)
- Phosphorylation
- Signal Transduction
- Zinc
(chemistry)
- tau Proteins
(chemistry)
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