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Target intelligence / Profile preview
Cyclic nucleotide phosphodiesterase 10A (PDE10A)
- Target
- PDE10A
- Molecular classification
- Enzyme, Phosphodiesterase family
01
Overview
Cyclic nucleotide phosphodiesterase 10A (PDE10A) is an enzyme predominantly expressed in striatal medium spiny neurons of the brain, where it hydrolyzes the intracellular second messengers cAMP and cGMP, thus terminating their signaling. PDE10A acts as a critical regulator of intracellular pathways involved in movement, cognition, and dopaminergic signaling. It is highly implicated in neuropsychiatric diseases, including schizophrenia, and is considered a promising therapeutic target for related disorders. PDE10A inhibitors have undergone extensive development for clinical use in neuropsychiatric diseases, though as of 2021, no inhibitor has achieved regulatory approval
- Other names
- PDE10APhosphodiesterase 10AcAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
02
Mechanism of action
Inhibition of PDE10A increases intracellular cAMP and cGMP levels, modulating downstream signaling in medium spiny neurons of the striatum
03
Biological functions
Hydrolysis of cAMP and cGMPRegulation of cyclic nucleotide signalingModulation of gene expression in striatal neurons
04
Disease associations
Neuropsychiatric disease (notably schizophrenia)Huntington diseaseParkinson diseaseObesity (potential link under investigation)
05
Safety considerations
Potential for long-term alterations to neuronal function and gene expressionUnknown effects in non-striatal tissues due to high selectivity of expression, but nonetheless requires monitoring
06
Interacting drugs
AMG-579
7 more in the full profile.
07
Biomarkers
Substance P mRNA (expression increased by PDE10A inhibition, marker for direct pathway MSNs)Enkephalin mRNA (expression increased, marker for indirect pathway MSNs)cfos expression (increased in response to PDE10A inhibition)
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