Adenosine A2A receptor gene disruption protects in an a-synuclein model of Parkinson's disease

被引：67

作者：

Kachroo, Anil

Schwarzschild, Michael A.

机构：

[1] Massachusetts Gen Hosp, Dept Neurol, MassGeneral Inst Neurodegenerat Dis, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

来源：

ANNALS OF NEUROLOGY | 2012年 / 71卷 / 02期

基金：

美国国家卫生研究院;

关键词：

HUMAN ALPHA-SYNUCLEIN; TRANSGENIC MICE; CAFFEINE; NEUROPROTECTION; PROTEASOME; INSIGHTS;

D O I：

10.1002/ana.22630

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 A2A receptor in knockout (KO) mice protects against dopaminergic neuron degeneration induced by a mutant human a-synuclein (hm2-aSYN) transgene containing both A53T and A30P. The A2A KO completely prevented loss of dopamine and dopaminergic neurons caused by the mutant a-synuclein transgene without altering levels of its expression. The adenosine A2A receptor appears required for neurotoxicity in a mutant a-synuclein model of PD. Together with prior studies the present findings indirectly support the neuroprotective potential of caffeine and more specific A2A antagonists. Ann Neurol 2012;71:278282

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收藏

页码：278 / 282

页数：5

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