Abstract | BACKGROUND:
Alzheimer's disease is a multifactorial disorder for which there is no disease-modifying treatment yet. CB2 receptors have emerged as a promising therapeutic target for Alzheimer's disease because they are expressed in neuronal and glial cells and their activation has no psychoactive effects. OBJECTIVE: The aim of this study was to investigate whether activation of the CB2 receptor would restore the aberrant enhanced proliferative activity characteristic of immortalized lymphocytes from patients with late-onset Alzheimer's disease. It is assumed that cell-cycle dysfunction occurs in both peripheral cells and neurons in patients with Alzheimer's disease, contributing to the instigation of the disease. METHODS: Lymphoblastoid cell lines from patients with Alzheimer's disease and age-matched control individuals were treated with a new, in-house-designed dual drug PGN33, which behaves as a CB2 agonist and butyrylcholinesterase inhibitor. We analyzed the effects of this compound on the rate of cell proliferation and levels of key regulatory proteins. In addition, we investigated the potential neuroprotective action of PGN33 in β- amyloid-treated neuronal cells. RESULTS: CONCLUSION: Our results suggest that the activation of CB2 receptors could be considered a useful therapeutic approach for Alzheimer's disease.
|
Authors | Patricia Del Cerro, Carolina Alquézar, Fernando Bartolomé, Pedro González-Naranjo, Concepción Pérez, Eva Carro, Juan A Páez, Nuria E Campillo, Ángeles Martín-Requero |
Journal | CNS drugs
(CNS Drugs)
Vol. 32
Issue 6
Pg. 579-591
(06 2018)
ISSN: 1179-1934 [Electronic] New Zealand |
PMID | 29736745
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- CNR2 protein, human
- Indazoles
- Neuroprotective Agents
- Receptor, Cannabinoid, CB2
- Proto-Oncogene Proteins c-akt
- Phosphopyruvate Hydratase
- Bromodeoxyuridine
|
Topics |
- Adult
- Aged
- Aged, 80 and over
- Alzheimer Disease
(drug therapy, metabolism, mortality, pathology)
- Animals
- Bromodeoxyuridine
(metabolism)
- Case-Control Studies
- Cell Line, Transformed
- Cell Proliferation
(drug effects)
- Cells, Cultured
- Dose-Response Relationship, Drug
- Embryo, Mammalian
- Female
- Humans
- Indazoles
(chemistry, pharmacology, therapeutic use)
- Lymphocytes
(drug effects)
- Male
- Middle Aged
- Neuroprotective Agents
(therapeutic use)
- Phosphopyruvate Hydratase
(metabolism)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Rats
- Rats, Wistar
- Receptor, Cannabinoid, CB2
(agonists, metabolism)
- Signal Transduction
(drug effects)
- Time Factors
|