PDE10A — Phosphodiesterase 10A

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

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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

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
• High: Olfactory tubercle, nucleus accumbens
• Moderate: [Cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), thalamus
• Low: Peripheral tissues

Key Publications

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/)

Beaumont V, et al. (2016). Phosphodiesterase 10A inhibition reduces Huntington's disease pathogenesis. Mol Psychiatry 21: 885-895. PMID: 26390828(https://pubmed.ncbi.nlm.nih.gov/26390828/)

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.

See Also

• [Phosphodiesterases](/entities/phosphodiesterases)
• [Huntington's Disease](/diseases/huntingtons-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [PDE10A Protein](/proteins/pde10a-protein)
• [Basal Ganglia](/brain-regions/basal-ganglia)

External Links

• [NCBI Gene: PDE10A](https://www.ncbi.nlm.nih.gov/gene/10846)
• [UniProt: O76074](https://www.uniprot.org/uniprot/O76074)
• [OMIM: 607341](https://www.omim.org/entry/607341)

References

[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: