Synaptotoxicity in Alzheimer's disease: the Wnt signaling pathway as a molecular target - PubMed (original) (raw)
Review
. 2007 Apr-May;59(4-5):316-21.
doi: 10.1080/15216540701242490.
Affiliations
- PMID: 17505971
- DOI: 10.1080/15216540701242490
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Review
Synaptotoxicity in Alzheimer's disease: the Wnt signaling pathway as a molecular target
Nibaldo C Inestrosa et al. IUBMB Life. 2007 Apr-May.
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Abstract
Recent evidence supports a role of the Wnt pathway in neurodegenerative disorders such as Alzheimer's disease (AD). A relationship between amyloid-beta-peptide (Abeta)-induced neurotoxicity and a decrease in the cytoplasmatic levels of beta-catenin has been proposed. Also, the inhibition of glycogen synthase kinase (GSK-3beta), a central modulator of the pathway, protects rat hippocampal neurons from Abeta-induced damage. Interestingly, during the progression of AD, it has been described that active GSK-3beta is found in neuronal cell bodies and neurites, co-localizing with pre-neurofibrillary tangles observed in disease brains. Since Abeta oligomers are associated with the post-synaptic region and we have found that the non-canonical Wnt signaling modulates PSD-95 and glutamate receptors, we propose that the synaptic target for Abeta oligomers in AD is the postsynaptic region and at the molecular level is the non-canonical Wnt signaling pathway. Altogether, our evidence suggests that a sustained loss of Wnt signaling function may be involved in the Abeta-dependent neurodegeneration observed in AD brains and that the activation of this signaling pathway could be of therapeutic interest in AD.
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