Title:Role of Adenosine Receptors in Rare Neurodegenerative Diseases with
Motor Symptoms
Volume: 22
Issue: 9
Author(s): Vicent Beltran-Beltran, Noelia Benetó, Tamara Lapeña-Luzón, Laura R. Rodríguez, Federico V. Pallardó and Pilar Gonzalez-Cabo*
Affiliation:
- Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia-INCLIVA, Valencia 46010,Spain
- Biomedical Research Institute INCLIVA, 46010 Valencia, Spain
- CIBER de Enfermedades Raras (CIBERER),
Valencia, Spain
Keywords:
adenosine receptors, Machado-Joseph disease, restless legs syndrome, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, neurodegeneration, rare diseases.
Abstract: The approval of istradefylline, an adenosine 2A receptor (A2AR) antagonist, as an addon
treatment in adult patients with Parkinson’s disease by the Food and Drug Administration (FDA)
and European Medicines Agency (EMA), is the latest proof of the importance of the adenosinergic
system in the nervous system. Adenosine is an endogenous purine nucleoside with a role as a modulator
of both neurotransmission and the inflammatory response. As such, the expression pattern of
the 4 adenosine receptors (A1R, A2AR, A2BR and A3R) and the extracellular adenosine levels
have attracted great interest in the pathogenesis and possible treatment of rare neurodegenerative
diseases with motor symptoms. These include Huntington’s Disease (HD), Amyotrophic Lateral
Sclerosis (ALS), Multiple Sclerosis (MS), Restless Legs Syndrome (RLS) and Machado-Joseph
Disease (MJD, also known as spinocerebellar ataxia type 3, SCA3). In this review, we shall focus
on the role of the different adenosine receptor subtypes in the development and possible treatment
of the aforementioned rare neurodegenerative diseases with motor symptoms using the currently
available data. The last section discusses the possibility of a role for the adenosine receptors in the
treatment of other rare diseases based on the available molecular pathology knowledge.
