Stimulation of @entity859 A2A receptors reduces intracellular XXXX accumulation and rescues mitochondrial abnormalities in @entity1 neural cell models of Niemann-Pick C1.

@entity2315 @entity1 @entity268 @entity859 @entity42123 @entity12176 @entity38153 @entity16 @entity11008 @entity828 @entity15997 @entity28569 @entity521 @entity460 @entity11408 @entity204 @entity165
UNASSIGNED: @entity38153 ( @entity38153 ) disease is an incurable, devastating @entity2315 characterized by @entity828 , progressive @entity16 and @entity204 . Current treatments are very limited and the research of new therapeutic targets is thus mandatory. We recently showed that the stimulation of @entity859 A2A receptors (A2ARs) rescues the abnormal phenotype of fibroblasts from @entity38153 @entity1 suggesting that @entity28569 agonists could represent a therapeutic option for this disease. However, since all @entity38153 @entity1 develop severe @entity16 which can be ascribed to the complex pathology occurring in both neurons and oligodendrocytes, in the present paper we tested the effects of the @entity28569 agonist @entity15997 in @entity1 neuronal and oligodendroglial @entity38153 cell lines (i.e. @entity521 SH-SY5Y and oligodendroglial MO3.13 transiently transfected with @entity38153 small interfering RNA). The down-regulation of the @entity38153 protein effectively resulted in intracellular @entity165 accumulation and altered mitochondrial membrane potential. Both effects were significantly attenuated by @entity15997 (500  nM). The protective effects of CGS were prevented by the selective @entity28569 antagonist @entity42123 (500  nM). The involvement of @entity460 modulation was demonstrated by the ability of @entity11008 (5-7   M) in reverting the effect of CGS. The A2A-dependent activity was prevented by the PKA-inhibitor @entity12176 , thus showing the involvement of the @entity268 /PKA signaling. These findings provide a clear in  vitro proof of concept that @entity28569 agonists are promising potential drugs for @entity11408 .
