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Aberrant A 2A receptor function in peripheral blood cells in Huntington's disease
Author(s) -
Varani Katia,
Abbracchio Maria P.,
Cannella Milena,
Cislaghi Giuliana,
Giallonardo Patrizia,
Mariotti Caterina,
Cattabriga Elena,
Cattabeni Flaminio,
Borea Pier Andrea,
Squitieri Ferdinando,
Cattaneo Elena
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0079fje
Subject(s) - huntingtin , huntington's disease , receptor , biology , adenosine a2a receptor , mutation , peripheral , medicine , disease , endocrinology , immunology , gene , adenosine receptor , genetics , agonist
A 2A 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 A 2A 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 A 2A 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. A 2A 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 A 2A 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.