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Silencing Phosphodiesterase 7B Gene by lentiviral-shRNA Interference Attenuates Neurodegeneration and Motor Deficits in Hemiparkinsonian Mice

Silencing Phosphodiesterase 7B Gene by lentiviral-shRNA Interference Attenuates Neurodegeneration and Motor Deficits in Hemiparkinsonian Mice

Jose A Morales-Garcia, Diana Aguilar-Morante, Elena Hernandez-Encinas, Sandra Alonso-Gil, Carmen Gil, Ana Martinez, Angel Santos, Ana Perez-Castillo

Neurobiol Aging. 2015 Feb;36(2):1160-73.

PMID: 25457552

Abstract:

Different studies have suggested that the nucleotide cyclic adenosine 3', 5'-monophosphate can actively play an important role as a neuroprotective and anti-inflammatory agent after a brain injury. The phosphodiesterase 7 (PDE7) enzyme is one of the enzymes responsible for controlling specifically the intracellular levels of cyclic adenosine 3', 5'-monophosphate 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's disease (PD). In the present study, we have used the toxin 6-hydroxydopamine and lipopolysaccharide 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-hydroxydopamine and lipopolysaccharide 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4245723	PDE7B active mouse			Price

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