Phosphodiesterase Inhibition Increases Striatal GDNF and Protects Against Preclinical Parkinsonism.

ABSTRACT: Glial cell line-derived neurotrophic factor (GDNF) has been investigated as a therapeutic agent for Parkinson's disease (PD), albeit with variable clinical outcomes. In the brain, GDNF is predominantly produced by striatal interneurons. Given that Gdnf gene expression is regulated by cyclic adenosine monophosphate (cAMP)-dependent signaling, a compelling strategy for PD treatment is the pharmacological elevation of intracellular cAMP. This approach aims to enhance endogenous GDNF, offering potential neuroprotective benefits. In this study, we show that selective inhibition of phosphodiesterases (PDEs) subtypes, therefore enhancing intracellular cAMP levels, increases Gdnf mRNA expression in striatal slices ex vivo; however, achieving this effect in vivo proved more challenging. To address

SUBMITTER: d'Anglemont de Tassigny X 

PROVIDER: S-EPMC12699109 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature