title: Adenosine A2A receptor gene disruption protects in an α-synuclein model of Parkinson's disease.
abstract: To investigate the putative interaction between chronic exposure to adenosine receptor antagonist caffeine and genetic influences on Parkinson's disease (PD), we determined whether deletion of the adenosine A(2A) receptor in knockout (KO) mice protects against dopaminergic neuron degeneration induced by a mutant human α-synuclein (hm(2)-αSYN) transgene containing both A53T and A30P. The A(2A) KO completely prevented loss of dopamine and dopaminergic neurons caused by the mutant α-synuclein transgene without altering levels of its expression. The adenosine A(2A) receptor appears required for neurotoxicity in a mutant α-synuclein model of PD. Together with prior studies the present findings indirectly support the neuroprotective potential of caffeine and more specific A(2A) antagonists.
authors.affiliation: MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Boston, USA. akachroo@partners.org
authors.forename: Anil
authors.initials: A
authors.lastname: Kachroo
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schwarzschild
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000627:therapeutic use; D000818:Animals; D002110:Caffeine / Q000627:therapeutic use; D004195:Disease Models, Animal; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D018696:Neuroprotective Agents; D043705:Receptor, Adenosine A2A; C497604:SNCA protein, human; C497605:Snca protein, mouse; D051844:alpha-Synuclein; D002110:Caffeine