Amyloid ß synaptotoxicity is Wnt-PCP dependent and blocked by fasudil.
Alzheimers Dement
; 14(3): 306-317, 2018 03.
Article
en En
| MEDLINE
| ID: mdl-29055813
ABSTRACT
INTRODUCTION:
Synapse loss is the structural correlate of the cognitive decline indicative of dementia. In the brains of Alzheimer's disease sufferers, amyloid ß (Aß) peptides aggregate to form senile plaques but as soluble peptides are toxic to synapses. We previously demonstrated that Aß induces Dickkopf-1 (Dkk1), which in turn activates the Wnt-planar cell polarity (Wnt-PCP) pathway to drive tau pathology and neuronal death.METHODS:
We compared the effects of Aß and of Dkk1 on synapse morphology and memory impairment while inhibiting or silencing key elements of the Wnt-PCP pathway.RESULTS:
We demonstrate that Aß synaptotoxicity is also Dkk1 and Wnt-PCP dependent, mediated by the arm of Wnt-PCP regulating actin cytoskeletal dynamics via Daam1, RhoA and ROCK, and can be blocked by the drug fasudil.DISCUSSION:
Our data add to the importance of aberrant Wnt signaling in Alzheimer's disease neuropathology and indicate that fasudil could be repurposed as a treatment for the disease.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sinapsis
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Péptidos beta-Amiloides
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Nootrópicos
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Fármacos Neuroprotectores
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1-(5-Isoquinolinesulfonil)-2-Metilpiperazina
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Vía de Señalización Wnt
Límite:
Animals
Idioma:
En
Revista:
Alzheimers Dement
Año:
2018
Tipo del documento:
Article
País de afiliación:
Reino Unido