title: Silencing phosphodiesterase 7B gene by lentiviral-shRNA interference attenuates neurodegeneration and motor deficits in hemiparkinsonian mice.
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.
authors.affiliation: Instituto de Investigaciones Biomédicas, (CSIC-UAM), Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Morales-Garcia
authors.affiliation: Instituto de Investigaciones Biomédicas, (CSIC-UAM), Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Aguilar-Morante
authors.affiliation: Instituto de Investigaciones Biomédicas, (CSIC-UAM), Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Hernandez-Encinas
authors.affiliation: Instituto de Investigaciones Biomédicas, (CSIC-UAM), Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Alonso-Gil
authors.affiliation: Centro de Investigaciones Biologicas, Biología FisicoQuimica, CSIC, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gil
authors.affiliation: Centro de Investigaciones Biologicas, Biología FisicoQuimica, CSIC, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Martinez
authors.affiliation: Departamento de Bioquímica y Biologia Molecular, Facultad de Medicina, UCM, Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Santos
authors.affiliation: Instituto de Investigaciones Biomédicas, (CSIC-UAM), Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. Electronic address: aperez@iib.uam.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Perez-Castillo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000502:physiology; D004660:Encephalitis / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D007107:Immune System / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D009043:Motor Activity / Q000235:genetics*; D009410:Nerve Degeneration / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D000242:Cyclic AMP; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517465:Pde7b protein, mouse
keywords: Inflammation; New target; Oxidative stress; PDE7B; Parkinson disease; shRNA