Adenosine receptors and Huntington's disease: implications for pathogenesis and therapeutics.
Huntington's disease (HD) is a devastating hereditary neurodegenerative disorder, the progression of which cannot be prevented by any neuroprotective approach, despite major advances in the understanding of its pathogenesis. The study of several animal models of the disease has led to the discovery of both loss-of-normal and gain-of-toxic functions of the mutated huntingtin protein and the elucidation of the mechanisms that underlie the formation of huntingtin aggregates and nuclear inclusions. Moreover, these models also provide good evidence of a role for excitotoxicity and mitochondrial metabolic impairments in striatal neuronal death. Adenosine has neuroprotective potential in both acute and chronic neurological disorders such as stroke or Parkinson's disease. Here we review experimental data on the role of A1 and A2A adenosine receptors in HD that warrant further investigation of the beneficial effects of A1 agonists and A2A antagonists in animal models of HD. Future pharmacological analysis of adenosine receptors could justify the use of A1 agonists and A2A antagonists for the treatment of HDin clinical trials.
Blum
David
D
Laboratory of Neurophysiology, Université Libre de Bruxelles, Belgium. dablum@ulb.ac.be
Hourez
Raphaël
R
Galas
Marie-Christine
MC
Popoli
Patrizia
P
Schiffmann
Serge N
SN
D000241:Adenosine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D058907:Adenosine A1 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D028361:Mitochondrial Diseases / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D008958:Models, Molecular; D008959:Models, Neurological; D009154:Mutation; D016571:Neural Networks, Computer; D018696:Neuroprotective Agents / Q000627:therapeutic use; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D011954:Receptors, Dopamine / Q000378:metabolism
D058907:Adenosine A1 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D018696:Neuroprotective Agents; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D011954:Receptors, Dopamine; D000241:Adenosine