title: Aberrant A2A receptor function in peripheral blood cells in Huntington's disease.
abstract: A2A adenosine receptors specifically found on striatal medium spiny neurons play a major role in sensory motor function and may also be involved in neuropsychiatric and neurodegenerative disorders. One hypothesis concerning Huntington's disease (HD) proposes that an imbalance of the cortico-striatal pathway, due to the mutation in the HD gene, leads to striatal vulnerability. An A2A receptor dysfunction has been previously demonstrated in striatal cells engineered to express mutant huntingtin. Here we tested whether a similar dysfunction (i.e., the binding and functional parameters of A2A adenosine receptors) is present in peripheral blood cells (platelets, lymphocytes, and neutrophils) of subjects carrying the mutant gene. This study involved 48 heterozygous and three homozygous patients compared with 58 healthy subjects. Moreover, we selected seven at-risk mutation carriers. A2A receptor density and function are substantially increased in peripheral blood cells from both patients and subjects at the presymptomatic stage. In the neutrophils of the three homozygous HD subjects receptor dysfunction was higher than in heterozygotes. These data indicate the existence of an aberrant A2A receptor phenotype in the peripheral blood cells of subjects carrying the HD mutation. Future studies will assess whether this parameter can be exploited as a peripheral biomarker of Huntington's disease.
authors.affiliation: Department of Clinical and Experimental Medicine, Pharmacology Unit, University of Ferrara, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.forename: Maria P
authors.initials: MP
authors.lastname: Abbracchio
authors.forename: Milena
authors.initials: M
authors.lastname: Cannella
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cislaghi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Giallonardo
authors.forename: Caterina
authors.initials: C
authors.lastname: Mariotti
authors.forename: Elena
authors.initials: E
authors.lastname: Cattabriga
authors.forename: Flaminio
authors.initials: F
authors.lastname: Cattabeni
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Squitieri
authors.forename: Elena
authors.initials: E
authors.lastname: Cattaneo
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D001773:Blood Cells / Q000737:chemistry / Q000378:metabolism*; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009504:Neutrophils / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D043705:Receptor, Adenosine A2A / Q000032:analysis / Q000502:physiology*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D043705:Receptor, Adenosine A2A; D000262:Adenylyl Cyclases