WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by A beta oligomers

Vargas J.Y.; Ahumada, J; Arrázola M.S.; Fuenzalida, M; Inestrosa, N. C.

Keywords: alzheimer's disease, wasp, wnt signaling, synaptic plasticity, 1, A? oligomers, Synaptic proteins

Abstract

Amyloid-β (Aβ) oligomers are a key factor in Alzheimer's disease (AD)-associated synaptic dysfunction. Aβ oligomers block the induction of hippocampal long-term potentiation (LTP) in rodents. The activation of Wnt signaling prevents Aβ oligomer-induced neurotoxic effects. The compound WASP-1 (Wnt-activating small molecule potentiator-1), has been described as a synergist of the ligand Wnt-3a, enhancing the activation of Wnt/β-catenin signaling. Herein, we report that WASP-1 administration successfully rescued Aβ-induced synaptic impairments both in vitro and in vivo. The activation of canonical Wnt/β-catenin signaling by WASP-1 increased synaptic transmission and rescued hippocampal LTP impairments induced by Aβ oligomers. Additionally, intra-hippocampal administration of WASP-1 to the double transgenic APPswe/PS1dE9 mouse model of AD prevented synaptic protein loss and reduced tau phosphorylation levels. Moreover, we found that WASP-1 blocked Aβ aggregation in vitro and reduced pathological tau phosphorylation in vivo. These results indicate that targeting canonical Wnt signaling with WASP-1 could have value for treating AD.

Más información

Título según WOS: WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by A beta oligomers
Título según SCOPUS: WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by A? oligomers
Título de la Revista: EXPERIMENTAL NEUROLOGY
Volumen: 264
Editorial: ACADEMIC PRESS INC ELSEVIER SCIENCE
Fecha de publicación: 2015
Página de inicio: 14
Página final: 25
Idioma: English
DOI:

10.1016/j.expneurol.2014.11.005

Notas: ISI, SCOPUS - ISI