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Title

Silencing phosphodiesterase 7B gene by lentiviral-shRNA interference attenuates neurodegeneration and motor deficits in hemiparkinsonian mice

AuthorsMorales-García, José A. ; Aguilar Morante, Diana ; Hernandez-Encinas, Elena; Alonso-Gil, Sandra ; Gil, Carmen ; Martínez, Ana ; Santos, Ángel; Pérez Castillo, Ana
KeywordsInflammation
New target
Oxidative stress
Parkinson disease
PDE7B
shRNA
Issue DateFeb-2015
PublisherElsevier
CitationNeurobiology of Aging 36(2): 1160–1173 (2015)
AbstractDifferent 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.
Description42 p.-10 fig.
Publisher version (URL)http://dx.doi.org/10.1016/j.neurobiolaging.2014.10.008
URIhttp://hdl.handle.net/10261/122641
DOI10.1016/j.neurobiolaging.2014.10.008
ISSN1087-1845
E-ISSN1096-0937
Appears in Collections:(IIBM) Artículos
(CIB) Artículos
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