PDE10A Protein — Dual-Specificity Phosphodiesterase 10A

PDE10A Protein — Dual-Specificity Phosphodiesterase 10A

Introduction

Pde10A Protein — Dual Specificity 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-protein"> [@mascarenhas2019]
| Attribute | Value | [@giampa2018]
|-----------|-------| [@menniti2006]
| Protein Name | Dual-Specificity Phosphodiesterase 10A | [@richter2013]
| Gene Encoding | PDE10A | [@bhandari2021]
| UniProt ID | O76074 | [@schmidt2008]
| PDB Structure | 3HR1, 4G2J | [@wilson2020]
| Molecular Weight | 79-82 kDa (isoform dependent) |
| Subcellular Localization | Cytosol |
| Protein Family | Phosphodiesterase 10 family |
| Associated Diseases | Huntington's Disease, Parkinson's Disease, Schizophrenia |
</div>

Overview

PDE10A is 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.

Structure

PDE10A contains:

• N-terminal regulatory region: Contains phosphorylation sites
• GAF domain: cGMP-binding domain (non-functional in PDE10A)
• Catalytic domain: C-terminal hydrolase domain

Isoforms:

• PDE10A1: Full-length, brain-enriched
• PDE10A2: Alternative splicing
• PDE10A3: Truncated isoform

Normal Function

...

PDE10A Protein — Dual-Specificity Phosphodiesterase 10A

Introduction

Pde10A Protein — Dual Specificity 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-protein"> [@mascarenhas2019]
| Attribute | Value | [@giampa2018]
|-----------|-------| [@menniti2006]
| Protein Name | Dual-Specificity Phosphodiesterase 10A | [@richter2013]
| Gene Encoding | PDE10A | [@bhandari2021]
| UniProt ID | O76074 | [@schmidt2008]
| PDB Structure | 3HR1, 4G2J | [@wilson2020]
| Molecular Weight | 79-82 kDa (isoform dependent) |
| Subcellular Localization | Cytosol |
| Protein Family | Phosphodiesterase 10 family |
| Associated Diseases | Huntington's Disease, Parkinson's Disease, schizophrenia |
</div>

Overview

PDE10A is 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.

Structure

PDE10A contains:

• N-terminal regulatory region: Contains phosphorylation sites
• GAF domain: cGMP-binding domain (non-functional in PDE10A)
• Catalytic domain: C-terminal hydrolase domain

Isoforms:

• PDE10A1: Full-length, brain-enriched
• PDE10A2: Alternative splicing
• PDE10A3: Truncated isoform

Normal Function

PDE10A has unique substrate specificity:

• cAMP: Primary substrate
• cGMP: Secondary substrate

In striatal neurons:

• Modulates MSN excitability
• Regulates motor control
• Integrates dopamine and glutamate signaling
• Controls basal ganglia output

Role in Disease

Huntington's Disease

• PDE10A highly expressed in striatum, affected in HD
• Expression decreases in HD models
• PDE10A inhibition improves motor function
• Clinical trials ongoing

Parkinson's Disease

• PDE10A regulates dopaminergic signaling
• Altered in PD substantia nigra
• Target for PD motor symptoms

Schizophrenia

• PDE10A is schizophrenia risk gene
• PDE10A inhibition has antipsychotic effects
• May modulate dopaminergic signaling

Therapeutic Targeting

PDE10A inhibitors in development:

• TP-10: Selective PDE10A inhibitor
• PF-2545920: Clinical candidate for HD
• MP-10: Improved PDE10A inhibitor

Therapeutic applications:

• Huntington's disease motor symptoms
• [Parkinson's disease](/diseases/parkinsons-disease) Schizophrenia (antipsychotic potential)

Key Publications

Fujishige K, et al. (1999). Cloning of PDE10A. J Biol Chem 274: 18438-18445. PMID: 10373449(https://pubmed.ncbi.nlm.nih.gov/10373449/)

Beaumont V, et al. (2016). PDE10A inhibition in HD. Mol Psychiatry 21: 885-895. PMID: 26390828(https://pubmed.ncbi.nlm.nih.gov/26390828/)

Wilson LS, et al. (2021). PDE10A mutations cause encephalopathy. Brain 144: 2006-2020. PMID: 33503276(https://pubmed.ncbi.nlm.nih.gov/33503276/)

Background

The study of Pde10A Protein — Dual Specificity 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

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

External Links

• [UniProt: O76074](https://www.uniprot.org/uniprot/O76074)
• [PDB: 3HR1](https://www.rcsb.org/structure/3HR1)
• [NCBI Protein: PDE10A](https://www.ncbi.nlm.nih.gov/protein/NP_001124167)

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/)

[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/)