# name
Epigenetic Modulation of Adenosine A2A Receptor: A Putative Therapeutical Tool for the Treatment of Parkinson’s Disease

# metadata.dc.description.abstract[].value
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 Gi/o protein, the A2Rs are
coupled in a stimulatory way to this enzymatic activity through Gs 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).

# metadata.dc.relation.ispartof[].value
Chapter 14 in: Finkelstein, David. 2011. Towards New Therapies for Parkinson's Disease. IntechOpen. ISBN: 978-953-51-6545-3. DOI: 10.5772/954. pp: 295-312.

# metadata.dc.rights[].value
cc by (c) Barrachina Castillo, Marta et al., 2011

# metadata.dc.source[].value
Llibres / Capítols de llibre (Patologia i Terapèutica Experimental)

# metadata.dc.title[].value
Epigenetic Modulation of Adenosine A2A Receptor: A Putative Therapeutical Tool for the Treatment of Parkinson’s Disease