Role of adenosine A(2A) receptors in modulating synaptic functions and brain levels of BDNF: a possible key mechanism in the pathophysiology of Huntington's disease.
In the last few years, accumulating evidence has shown the existence of an important cross-talk between adenosine A(2A) receptors (A(2A)Rs) and brain-derived neurotrophic factor (BDNF). Not only are A(2A)Rs involved in the mechanism of transactivation of BDNF receptor TrkB, they also modulate the effect of BDNF on synaptic transmission, playing a facilitatory and permissive role. The cAMP-PKA pathway, the main transduction system operated by A(2A)Rs, is involved in such effects. Furthermore, a basal tonus of A(2A)Rs is required to allow the regulation of BDNF physiological levels in the brain, as demonstrated by the reduced protein levels measured in A(2A)Rs KO mice. The crucial role of adenosine A(2A)Rs in the maintenance of synaptic functions and BDNF levels will be reviewed here and discussed in the light of possible implications for Huntington's disease therapy, in which a joint impairment of BDNF and A(2A)Rs seems to play a pathogenetic role.
Tebano
Maria Teresa
MT
Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome. mariateresa.tebano@iss.it
Martire
Alberto
A
Chiodi
Valentina
V
Ferrante
Antonella
A
Popoli
Patrizia
P
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism / Q000503:physiopathology; D008959:Models, Neurological; D043705:Receptor, Adenosine A2A / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D043705:Receptor, Adenosine A2A; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases