Epigenetic Modulation of Adenosine A2A Receptor: A Putative Therapeutical Tool for the Treatment of Parkinson’s Disease
Adenosine is a nucleoside distributed throughout the entire organism as an intermediary metabolite. At the extracellular level, adenosine plays multiple physiologic roles, interacting with specific receptors: A1, A2A, A2B and A3 (Fredholm et al., 2001). While the A1Rs and A3Rs are coupled in an inhi...
| Autores: | , , , |
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| Formato: | capítulo de livro |
| Estado: | Versión publicada |
| Fecha de publicación: | 2011 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/178792 |
| Acesso em linha: | https://hdl.handle.net/2445/178792 |
| Access Level: | acceso abierto |
| Palavra-chave: | Malaltia d'Alzheimer Terapèutica Alzheimer's disease Therapeutics |
| Resumo: | Adenosine is a nucleoside distributed throughout the entire organism as an intermediary metabolite. At the extracellular level, adenosine plays multiple physiologic roles, interacting with specific receptors: A1, A2A, A2B and A3 (Fredholm et al., 2001). While the A1Rs and A3Rs are coupled in an inhibitory way to adenylate cyclase through the Gi/o protein, the A2Rs are coupled in a stimulatory way to this enzymatic activity through Gs protein (Ralevic & Burnstock, 1998). Adenosine levels are increased after ischemia, hypoxia, excitotoxicity, inflammation and cerebral lesions. In these situations, it is considered that high adenosine levels play a neuroprotective role (Ribeiro et al., 2002). Interestingly, adenosine regulates the release of glutamate, the main excitatory neurotransmitter of the nervous system (Sebastiao & Ribeiro, 1996). A1Rs are widely expressed in the brain and have been shown to modulate neuronal excitability by decreasing pre-synaptic release of various neurotransmitters (Fredholm & Dunwiddie, 1988). The most dramatic inhibitory actions are on the glutamatergic system (Masino et al., 2002). In the central nervous system (CNS), A1Rs are associated with neuroprotective processes (Angulo et al., 2003; Dunwiddie and Masino, 2001). Moreover, they are upregulated in human neurodegenerative diseases with abnormal protein aggregates and it is related to compensatory mechanisms (Albasanz et al., 2007, 2008; Angulo et al., 2003; Perez-Buira et al., 2007; Rodríguez et al., 2006). Regarding A2ARs, these receptors are concentrated in the striatum, modulating dopaminergic activity, but they are also present in the hippocampus and cerebral cortex, modulating the glutamate release in the brain. Adenosine activity through A2 receptors (A2ARs) can eventually give rise to neurotoxicity, neuronal damage and cellular death (de Mendoça et al., 2000). In fact, A2ARs activity is associated with the outcome of cerebral injury as well as the development of Abeta- induced synaptotoxicity (Canas et al., 2009; Cunha, 2005; Stone et al., 2009). |
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