TY - JOUR
T1 - 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
AU - Maccarrone, Mauro
AU - Totaro, Antonio
AU - Leuti, Alessandro
AU - Giacovazzo, Giacomo
AU - Scipioni, Lucia
AU - Mango, Dalila
AU - Coccurello, Roberto
AU - Nisticò, Robert
AU - Oddi, Sergio
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Amyloid precursor protein
KW - Cannabinoid receptor
KW - Hippocampus
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=85042222810&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042222810&partnerID=8YFLogxK
U2 - 10.1016/j.phrs.2018.02.009
DO - 10.1016/j.phrs.2018.02.009
M3 - Article
AN - SCOPUS:85042222810
JO - Pharmacological Research
JF - Pharmacological Research
SN - 1043-6618
ER -