Acetylcholinesterase (AChE) - Amyloid-β-Peptide Complexes in Alzheimers Disease. The Wnt Signaling Pathway

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.

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