Adenosine receptors in Huntington's disease

Abstract

Huntington's disease is a devastating hereditary neurodegenerative disorder caused by CAG mutation within the IT15 gene encoding Huntingtin protein. Even though mutant and normal Huntingtin are ubiquitously expressed, the degenerative processes primarily occur within the striatum and particularly hit the GABAergic enkephalin neuronal subpopulation of medium spiny neurons particularly enriched with adenosine A 2A Rs, suggesting that the latter might play a role in HD. In agreement, variants in the ADORA2A gene influence the age at onset in HD and A 2A R dynamics is largely altered by mutated Huntingtin. Adenosine receptors are involved in a number of processes critical for neuronal function and homeostasis, such as modulation of synaptic activity and excitotoxicity, the control of neurotrophin levels and functions as well as the regulation of protein degradation mechanisms. In the present review, we critically reviewed the current knowledge involving adenosine receptors in HD and discussed whether they represent a suitable therapeutic target.