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Phosphodiesterases (PDEs) are expressed in different brain areas including the striatum. PDEs have recently emerged as important drug targets for central nervous system disorders, including Parkinson’s disease (PD). Levels of cyclic adenosine monophosphate (cAMP) control many cellular signaling pathways and are crucial for the dopamine signal, which is disturbed in PD due to the progressive loss of dopaminergic neurons. PDEs play a key role in cAMP homeostasis, as they are the enzymes responsible for its degradation. Moreover, beyond dopamine neurotransmission, cAMP is involved in many other cellular processes, such as neuroinflammation and neuronal plasticity. This enhances the value of PDEs as promising pharmacological targets for neurological disorders. Furthermore, cAMP‐PDE inhibitors with drug profiles may be used in the near future as disease‐modifying drugs for the treatment of PD. A concise review of the main roles of cAMP‐PDEs expressed in the striatum and the potential of their inhibitors in different animal models of PD is described in this chapter.

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