Abstract
Alzheimers disease (AD) is characterized by selective neuronal cell death, which is probably caused by amyloid b-peptide (Aβ) oligomers and fibrils. We have found that acetylcholinesterase (AChE), a senile plaque component, increases amyloid fibril assembly with the formation of highly toxic complexes (Aβ-AChE). The neurotoxic effect induced by Aβ-AChE complexes was higher than that induced by the Aβ peptide alone as shown both in vitro (hippocampal neurons) and in vivo (rats injected with Ab peptide in the dorsal hippocampus). Interestingly, treatment with Aβ-AChE complexes decreases the cytoplasmic β-catenin level, a key component of Wnt signaling. Conversely, the activation of this signaling pathway by Wnt-3a promotes neuronal survival and rescues changes in Wnt components (activation or subcellular localization). Moreover Frzb-1, a Wnt antagonist reverses the Wnt-3a neuroprotection effect against Aβ neurotoxicity. Compounds that mimic the Wnt signaling or modulate the cross-talking with this pathway could be used as neuroprotective agents for therapeutic strategies in AD patients.
Keywords: ache activity, neurodegenerative processes, brain, amyloid fibrils, hippocampal neurons, signaling pathway, g-catenin, gsk
Current Alzheimer Research
Title: Acetylcholinesterase (AChE) - Amyloid-β-Peptide Complexes in Alzheimers Disease. The Wnt Signaling Pathway
Volume: 1 Issue: 4
Author(s): Nibaldo C. Inestrosa, Soledad Urra and Marcela Colombres
Affiliation:
Keywords: ache activity, neurodegenerative processes, brain, amyloid fibrils, hippocampal neurons, signaling pathway, g-catenin, gsk
Abstract: Alzheimers disease (AD) is characterized by selective neuronal cell death, which is probably caused by amyloid b-peptide (Aβ) oligomers and fibrils. We have found that acetylcholinesterase (AChE), a senile plaque component, increases amyloid fibril assembly with the formation of highly toxic complexes (Aβ-AChE). The neurotoxic effect induced by Aβ-AChE complexes was higher than that induced by the Aβ peptide alone as shown both in vitro (hippocampal neurons) and in vivo (rats injected with Ab peptide in the dorsal hippocampus). Interestingly, treatment with Aβ-AChE complexes decreases the cytoplasmic β-catenin level, a key component of Wnt signaling. Conversely, the activation of this signaling pathway by Wnt-3a promotes neuronal survival and rescues changes in Wnt components (activation or subcellular localization). Moreover Frzb-1, a Wnt antagonist reverses the Wnt-3a neuroprotection effect against Aβ neurotoxicity. Compounds that mimic the Wnt signaling or modulate the cross-talking with this pathway could be used as neuroprotective agents for therapeutic strategies in AD patients.
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Cite this article as:
Inestrosa C. Nibaldo, Urra Soledad and Colombres Marcela, Acetylcholinesterase (AChE) - Amyloid-β-Peptide Complexes in Alzheimers Disease. The Wnt Signaling Pathway, Current Alzheimer Research 2004; 1 (4) . https://dx.doi.org/10.2174/1567205043332063
DOI https://dx.doi.org/10.2174/1567205043332063 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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