Regulation of Striatal Neuron Activity by Cyclic Nucleotide Signaling and Phosphodiesterase Inhibition: Implications for the Treatment of Parkinson's Disease.

摘要: Cyclic nucleotide phosphodiesterase (PDE) enzymes catalyze the hydrolysis and inactivation of cyclic nucleotides (cAMP/cGMP) in brain. Several classes PDE with distinct tissue distributions, selectivity, regulatory factors are highly expressed brain regions subserving cognitive motor processes known to be disrupted neurodegenerative diseases such as Parkinson’s disease (PD). Furthermore, small-molecule inhibitors several different family members alter levels favorably enhance performance cognition animal models. This chapter will explore roles therapeutic potential non-selective selective on neural processing fronto-striatal circuits normal animals models DOPA-induced dyskinesias (LIDs) associated PD. The impact augmentation cAMP cGMP signaling membrane excitability striatal medium-sized spiny projection neurons (MSNs) discussed. effects synaptic plasticity striatonigral striatopallidal MSNs also reviewed. New data efficacy PDE10A for reversing behavioral electrophysiological correlates L-DOPA-induced a rat model PD presented. Together, these highlight novel treatment movement disorders which abnormal corticostriatal transmission.