Early alteration of distribution and activity of hippocampal type-1 cannabinoid receptor in Alzheimer's disease-like mice overexpressing the human mutant amyloid precursor protein.
Pharmacol Res
; 130: 366-373, 2018 04.
Article
en En
| MEDLINE
| ID: mdl-29454025
ABSTRACT
Besides its involvement in Alzheimer's disease (AD) as precursor of the neurotoxic amyloid peptides, the pathophysiological impact of brain accumulation of amyloid precursor protein (APP) is not yet well understood. Recent studies reported that APP interacts with other membrane proteins, including G protein coupled receptors, affecting their biological functions. Here, we focused on the study of the potential impact of human mutant APP on expression, distribution and activity of type-1 cannabinoid (CB1) receptor in the hippocampus of Tg2576 mice, an AD-like mice model. By using biochemical and electrophysiological measures, we found that in a presymptomatic phase, when amyloid plaques have not yet formed and there is no sign of cognitive deficits, the over-expression of full-length APP in the hippocampus of Tg2576 mice altered membrane localization and inhibitory signalling activity of CB1 receptor, possibly by binding to the receptor and reducing its specific interaction with caveolin-1 and G proteins.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Precursor de Proteína beta-Amiloide
/
Receptor Cannabinoide CB1
/
Enfermedad de Alzheimer
/
Hipocampo
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Pharmacol Res
Asunto de la revista:
FARMACOLOGIA
Año:
2018
Tipo del documento:
Article