Pde10A — Phosphodiesterase 10A is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox .infobox-gene"> [@mascarenhas2019] | Attribute | Value | [@giampa2018] |-----------|-------| [@menniti2006] | Gene Symbol | PDE10A | [@richter2013] | Full Name | Phosphodiesterase 10A | [@bhandari2021] | Chromosomal Location | 6q27 | [@heckman2020] | NCBI Gene ID | 10846 | [@schmidt2008] | OMIM ID | 607341 | [@wilson2020] | Ensembl ID | ENSG00000112541 | [@padovani2021] | UniProt ID | O76074 | [@cosgrove2011] | Encoded Protein | Dual-Specificity Phosphodiesterase 10A | [@silverman2012] | Associated Diseases | Huntington's Disease, Parkinson's Disease, Schizophrenia, Infantile Epileptic Encephalopathy | </div>
Overview
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PDE10A — Phosphodiesterase 10A
Introduction
Pde10A — Phosphodiesterase 10A is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox .infobox-gene"> [@mascarenhas2019] | Attribute | Value | [@giampa2018] |-----------|-------| [@menniti2006] | Gene Symbol | PDE10A | [@richter2013] | Full Name | Phosphodiesterase 10A | [@bhandari2021] | Chromosomal Location | 6q27 | [@heckman2020] | NCBI Gene ID | 10846 | [@schmidt2008] | OMIM ID | 607341 | [@wilson2020] | Ensembl ID | ENSG00000112541 | [@padovani2021] | UniProt ID | O76074 | [@cosgrove2011] | Encoded Protein | Dual-Specificity Phosphodiesterase 10A | [@silverman2012] | Associated Diseases | Huntington's Disease, Parkinson's Disease, Schizophrenia, Infantile Epileptic Encephalopathy | </div>
Overview
Mermaid diagram (expand to render)
PDE10A encodes a dual-specificity phosphodiesterase that hydrolyzes both cAMP and cGMP. It is highly enriched in striatal medium spiny [neurons](/entities/neurons) (MSNs), making it a unique therapeutic target for basal ganglia disorders.
Function
PDE10A has unique substrate specificity:
cAMP hydrolysis: Primary substrate
cGMP hydrolysis: Secondary substrate
Dual-specificity: Rare among PDE family members
Regulation:
Basal activity: High constitutive activity
Phosphorylation: Can be regulated by PKA
Cellular localization: Primarily cytosolic
Key neuronal functions:
Striatal signaling: Critical regulator of MSN excitability
Motor control: Modulates basal ganglia output
Reward processing: Dopamine D1 receptor signaling
Learning: cAMP dynamics in striatum
Disease Associations
Huntington's Disease
PDE10A is highly expressed in striatum, affected in HD.
PDE10A expression decreases in HD mouse models.
PDE10A inhibition improves motor function in HD models.
Clinical trials for HD with PDE10A inhibitors ongoing.
Parkinson's Disease
PDE10A regulates dopaminergic signaling in striatum.
Altered PDE10A in PD substantia nigra.
Potential target for PD motor symptoms.
Schizophrenia
PDE10A is a risk gene for schizophrenia.
PDE10A inhibitors have antipsychotic-like effects.
May modulate dopaminergic and glutamatergic signaling.
Infantile Epileptic Encephalopathy
Biallelic PDE10A mutations cause early infantile epileptic encephalopathy 47.
Characterized by seizures, developmental delay, movement disorders.
Loss of PDE10A function disrupts neuronal cAMP homeostasis.
Expression Pattern
PDE10A has highly specific expression:
Very high: Striatum (caudate nucleus, putamen) - medium spiny neurons
Fujishige K, et al. (1999). Cloning and characterization of a novel human phosphodiesterase. J Biol Chem 274: 18438-18445. PMID: 10373449(https://pubmed.ncbi.nlm.nih.gov/10373449/)
Wilson LS, et al. (2021). PDE10A mutations cause infantile encephalopathy. Brain 144: 2006-2020. PMID: 33503276(https://pubmed.ncbi.nlm.nih.gov/33503276/)
Background
The study of Pde10A — Phosphodiesterase 10A has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
[Thomazeau A, et al, (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/25404934/)
[Mascarenhas F, et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/30729921/)
[Giampa C, et al, (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29486297/)
[Menniti FS, et al, (2006) (2006)](https://pubmed.ncbi.nlm.nih.gov/16816838/)
[Richter W, et al, (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/22710435/)
[Bhandari R, et al, (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/33118762/)
[Heckman PR, et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/33192454/)
[Schmidt CJ, et al, (2008) (2008)](https://pubmed.ncbi.nlm.nih.gov/18299713/)
[Wilson LS, et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32779742/)
[Padovani L, et al, (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/33793728/)
[Cosgrove KP, et al, (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/21852374/)
[Unknown, Silverman RB (2012). The potential for phosphodiesterase 10A inhibitors in the treatment of neurodegenerative diseases. Trends Pharmacol Sci 33: 456-467 (2012)](https://pubmed.ncbi.nlm.nih.gov/22784897/)
Pathway Diagram
The following diagram shows the key molecular relationships involving PDE10A — Phosphodiesterase 10A discovered through SciDEX knowledge graph analysis: