1 research outputs found
Silencing phosphodiesterase 7B gene by lentiviral-shRNA interference attenuates neurodegeneration and motor deficits in hemiparkinsonian mice
42 p.-10 fig.Different studies have suggested that the nucleotide cyclic adenosine 3’, 5’-
monophosphate (cAMP) can actively play an important role as neuroprotective and antiinflammatory agent after a brain injury. The phosphodiesterase 7 (PDE7) enzyme is
one of the enzymes responsible for controlling specifically the intracellular levels of
cAMP in the immune and central nervous systems. Therefore this enzyme could play an important role in brain inflammation and neurodegeneration. In this regard, using
different chemical inhibitors of PDE7 we have demonstrated their neuroprotective and
anti-inflammatory activity in different models of neurodegenerative disorders, including
Parkinson disease (PD). In the present study, we have used the toxin 6-
hydroxydopamine (6-OHDA) and lipopolysaccharide (LPS) to model PD and explore
the protective effects of PDE7B deficiency in dopaminergic neurons cell death.
Lentivirus-mediated PDE7B deprivation conferred marked in vitro and in vivo
neuroprotection against 6-OHDA and LPS toxicity in dopaminergic neurons, and
preserved motor function involving the dopamine system in mouse. Our results
substantiate previous data and provide a validation of PDE7B enzyme as a valuable new target for therapeutic development in the treatment of PD.The authors gratefully acknowledge the financial support of MICINN (Grant SAF2010-16365, to A.P-C and GrantSAF2012-33600, to C.G.). CIBERNED is funded by the Instituto de Salud Carlos III.Peer reviewe