Tags

Type your tag names separated by a space and hit enter

The activation of cannabinoid CB2 receptors stimulates in situ and in vitro beta-amyloid removal by human macrophages.
Brain Res. 2009 Aug 04; 1283:148-54.BR

Abstract

The endocannabinoid system is a promising therapeutic target in a wide variety of diseases. However, the non-desirable psychotropic effects of natural and synthetic cannabinoids have largely counteracted their clinical usefulness. These effects are mostly mediated by cannabinoid receptors of the CB(1) type, that exhibit a wide distribution in neuronal elements of the CNS. Thus, the presence of other elements of this system in the CNS, such as CB(2) receptors, may open new possibilities for the development of cannabinoid-based therapies. These receptors are almost absent from the CNS in normal conditions but are up-regulated in glial cells under chronic neuroinflammatory stimuli, as has been described in Alzheimer's disease. To understand the functional role of these receptors, we tested their role in the process of beta-amyloid removal, that is currently considered as one of the most promising experimental approaches for the treatment of this disease. Our results show that a CB(2) agonist (JWH-015) is capable of inducing the removal of native beta-amyloid removal from human frozen tissue sections as well as of synthetic pathogenic peptide by a human macrophage cell line (THP-1). Remarkably, this effect was achieved at low doses (maximum effect at 10 nM) and was specific for this type of cells, as U373MG astrocytoma cells did not respond to the treatment. The effect was CB(2)-mediated, at least partially, as the selective CB(2) antagonist SR144528 prevented the JWH-015-induced plaque removal in situ. These data corroborate the possible therapeutic interest of CB(2) cannabinoid specific chemicals in the treatment of Alzheimer's disease.

Authors+Show Affiliations

Laboratorio de Apoyo a la Investigación, Hospital Universitario Fundación Alcorcón and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, 28922 Alcorcón, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19505450

Citation

Tolón, Rosa María, et al. "The Activation of Cannabinoid CB2 Receptors Stimulates in Situ and in Vitro Beta-amyloid Removal By Human Macrophages." Brain Research, vol. 1283, 2009, pp. 148-54.
Tolón RM, Núñez E, Pazos MR, et al. The activation of cannabinoid CB2 receptors stimulates in situ and in vitro beta-amyloid removal by human macrophages. Brain Res. 2009;1283:148-54.
Tolón, R. M., Núñez, E., Pazos, M. R., Benito, C., Castillo, A. I., Martínez-Orgado, J. A., & Romero, J. (2009). The activation of cannabinoid CB2 receptors stimulates in situ and in vitro beta-amyloid removal by human macrophages. Brain Research, 1283, 148-54. https://doi.org/10.1016/j.brainres.2009.05.098
Tolón RM, et al. The Activation of Cannabinoid CB2 Receptors Stimulates in Situ and in Vitro Beta-amyloid Removal By Human Macrophages. Brain Res. 2009 Aug 4;1283:148-54. PubMed PMID: 19505450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The activation of cannabinoid CB2 receptors stimulates in situ and in vitro beta-amyloid removal by human macrophages. AU - Tolón,Rosa María, AU - Núñez,Estefanía, AU - Pazos,María Ruth, AU - Benito,Cristina, AU - Castillo,Ana Isabel, AU - Martínez-Orgado,José Antonio, AU - Romero,Julián, Y1 - 2009/06/06/ PY - 2009/04/07/received PY - 2009/05/22/revised PY - 2009/05/27/accepted PY - 2009/6/10/entrez PY - 2009/6/10/pubmed PY - 2009/10/24/medline SP - 148 EP - 54 JF - Brain research JO - Brain Res. VL - 1283 N2 - The endocannabinoid system is a promising therapeutic target in a wide variety of diseases. However, the non-desirable psychotropic effects of natural and synthetic cannabinoids have largely counteracted their clinical usefulness. These effects are mostly mediated by cannabinoid receptors of the CB(1) type, that exhibit a wide distribution in neuronal elements of the CNS. Thus, the presence of other elements of this system in the CNS, such as CB(2) receptors, may open new possibilities for the development of cannabinoid-based therapies. These receptors are almost absent from the CNS in normal conditions but are up-regulated in glial cells under chronic neuroinflammatory stimuli, as has been described in Alzheimer's disease. To understand the functional role of these receptors, we tested their role in the process of beta-amyloid removal, that is currently considered as one of the most promising experimental approaches for the treatment of this disease. Our results show that a CB(2) agonist (JWH-015) is capable of inducing the removal of native beta-amyloid removal from human frozen tissue sections as well as of synthetic pathogenic peptide by a human macrophage cell line (THP-1). Remarkably, this effect was achieved at low doses (maximum effect at 10 nM) and was specific for this type of cells, as U373MG astrocytoma cells did not respond to the treatment. The effect was CB(2)-mediated, at least partially, as the selective CB(2) antagonist SR144528 prevented the JWH-015-induced plaque removal in situ. These data corroborate the possible therapeutic interest of CB(2) cannabinoid specific chemicals in the treatment of Alzheimer's disease. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/19505450/The_activation_of_cannabinoid_CB2_receptors_stimulates_in_situ_and_in_vitro_beta_amyloid_removal_by_human_macrophages_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(09)01134-2 DB - PRIME DP - Unbound Medicine ER -