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Phosphodiesterase 7 inhibition induces dopaminergic neurogenesis in hemiparkinsonian rats

AuthorsMorales-García, José A. ; Alonso-Gil, Sandra ; Gil, Carmen ; Martínez, Ana ; Santos, Ángel; Pérez Castillo, Ana
KeywordsDopaminergic differentiation
Parkinson disease
Phosphodiesterase 7
Issue Date30-Jun-2015
PublisherAlphaMed Press
CitationStem Cells Translational Medicine 4(6): 564-575 (2015)
AbstractParkinson’s disease is characterized by a loss of dopaminergic neurons in a specific brain region, the ventral midbrain. Parkinson’s disease is diagnosed when about 50% of the dopaminergic neurons of the substantia nigra pars compacta (SNpc) have degenerated and the others are already affected by the disease. Thus, it is conceivable that all therapeutic strategies, aimed at neuroprotection, start too late. Therefore there is an urgent medical need to discover new pharmacological targets and novel drugs with disease-modifying properties. In this regard, modulation of endogenous adult neurogenesis towards a dopaminergic phenotype may provide a new strategy to target Parkinson’s disease by partially ameliorating the dopaminergic cell loss that takes place in this disorder. We have previously shown that a PDE7 inhibitor called S14 exerts potent neuroprotective and anti-inflammatory effects in different rodent models of Parkinson’s disease indicating that this compound could represent a novel therapeutic agent to stop the dopaminergic cell loss that takes place during the progression of the disease. In this paper we show that, in addition to its neuroprotective effect, the PDE7 inhibitor S14 is also able to induce endogenous neuroregenerative processes towards a dopaminergic phenotype. We here describe a population of actively dividing cells, which give rise to new neurons in the SNpc of hemiparkinsonian rats after treatment with S14. In summary, our data identify S14 as a novel regulator of dopaminergic neuron generation.
Description44 p.-7 fig.-1 fig. supl.
Publisher version (URL)http://dx.doi.org/ 10.5966/sctm.2014-0277
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