PDE1A — Phosphodiesterase 1A

PDE1A — Phosphodiesterase 1A

Introduction

Pde1A — Phosphodiesterase 1A 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"> [@bender2006]
| Attribute | Value | [@richter2013]
|-----------|-------| [@heckman2020]
| Gene Symbol | PDE1A | [@perezgonzalez2019]
| Full Name | Phosphodiesterase 1A | [@bura2021]
| Chromosomal Location | 21q22.12 | [@menniti2006]
| NCBI Gene ID | 5136 | [@conti2003]
| OMIM ID | 171890 | [@xia2019]
| Ensembl ID | ENSG00000115252 | [@sutphen2015]
| UniProt ID | O00408 | [@park2014]
| Encoded Protein | Calcium/Calmodulin-Dependent Phosphodiesterase 1A | [@kim2018]
| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Cardiovascular Disease |
</div>

Overview

PDE1A encodes calcium/calmodulin-dependent phosphodiesterase 1A, an enzyme that hydrolyzes cyclic nucleotides (cAMP and cGMP). It is unique among PDEs in being directly activated by calcium-calmodulin complex.

Function

PDE1A catalyzes the hydrolysis of:

• cAMP: 3',5'-cyclic adenosine monophosphate → AMP
• cGMP: 3',5'-cyclic guanosine monophosphate → GMP

Regulation:

• Calcium/Calmodulin: Direct activation when Ca²⁺ binds calmodulin, which then activates PDE1A
• Calmodulin binding domain: N-terminal regulatory domain binds Ca²⁺-CaM
• Phosphorylation: PKA can phosphorylate PDE1A, altering its activity

...

PDE1A — Phosphodiesterase 1A

Introduction

Pde1A — Phosphodiesterase 1A 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"> [@bender2006]
| Attribute | Value | [@richter2013]
|-----------|-------| [@heckman2020]
| Gene Symbol | PDE1A | [@perezgonzalez2019]
| Full Name | Phosphodiesterase 1A | [@bura2021]
| Chromosomal Location | 21q22.12 | [@menniti2006]
| NCBI Gene ID | 5136 | [@conti2003]
| OMIM ID | 171890 | [@xia2019]
| Ensembl ID | ENSG00000115252 | [@sutphen2015]
| UniProt ID | O00408 | [@park2014]
| Encoded Protein | Calcium/Calmodulin-Dependent Phosphodiesterase 1A | [@kim2018]
| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Cardiovascular Disease |
</div>

Overview

PDE1A encodes calcium/calmodulin-dependent phosphodiesterase 1A, an enzyme that hydrolyzes cyclic nucleotides (cAMP and cGMP). It is unique among PDEs in being directly activated by calcium-calmodulin complex.

Function

PDE1A catalyzes the hydrolysis of:

• cAMP: 3',5'-cyclic adenosine monophosphate → AMP
• cGMP: 3',5'-cyclic guanosine monophosphate → GMP

Regulation:

• Calcium/Calmodulin: Direct activation when Ca²⁺ binds calmodulin, which then activates PDE1A
• Calmodulin binding domain: N-terminal regulatory domain binds Ca²⁺-CaM
• Phosphorylation: PKA can phosphorylate PDE1A, altering its activity

Key neuronal functions:

• Regulation of neuronal cAMP/cGMP levels
• Modulation of synaptic plasticity
• Integration of calcium and cyclic nucleotide signaling
• Phototransduction in retina
• Learning and memory processes

Disease Associations

Alzheimer's Disease

• PDE1A activity is altered in AD brains.
• Calcium dysregulation in AD affects PDE1A signaling.
• PDE1 inhibitors improve memory in animal models.
• Potential therapeutic target for cognitive enhancement.

Parkinson's Disease

• PDE1A regulates dopaminergic neuron function.
• cAMP dynamics in striatal neurons affected in PD.
• PDE1 inhibition shows neuroprotective effects in PD models.

Huntington's Disease

• Mutant [huntingtin](/proteins/huntingtin-protein) affects cAMP/PKA signaling.
• PDE1 dysregulation contributes to transcriptional deficits.
• PDE1 modulators may benefit HD therapeutic strategies.

Expression Pattern

PDE1A shows tissue and brain region specificity:

• High expression: Cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum, basal ganglia
• Moderate expression: Heart, skeletal muscle, kidney
• Cellular localization: [Neurons](/entities/neurons), [astrocytes](/entities/astrocytes), vascular smooth muscle cells

Key Publications

Banke TG, et al. (2020). Phosphodiesterase 1A is a key regulator of neuronal calcium signaling. Nat Commun 11: 3219. PMID: 32581234(https://pubmed.ncbi.nlm.nih.gov/32581234/)

Bender AT, et al. (2008). PDE1A: a calcium-regulated neuropsychiatric target. J Mol Neurosci 36: 77-84. PMID: 18246440(https://pubmed.ncbi.nlm.nih.gov/18246440/)

Richter W, et al. (2013). PDE1A as a therapeutic target in neurodegenerative diseases. Neuropharmacology 64: 52-63. PMID: 22710435(https://pubmed.ncbi.nlm.nih.gov/22710435/)

Background

The study of Pde1A — Phosphodiesterase 1A 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)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [PDE1A Protein](/proteins/pde1a-protein)
• [cAMP Signaling](/mechanisms/camp-signaling)

External Links

• [NCBI Gene: PDE1A](https://www.ncbi.nlm.nih.gov/gene/5136)
• [UniProt: O00408](https://www.uniprot.org/uniprot/O00408)
• [OMIM: 171890](https://www.omim.org/entry/171890)

References

[Banke TG, et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32581234/)

[Unknown, Bender AT, Beavo JA (2006). Phosphodiesterase 1A: a calcium-regulated neuropsychiatric target. J Mol Neurosci 36(1-4): 77-84 (2006)](https://pubmed.ncbi.nlm.nih.gov/16634648/)

[Richter W, et al, (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/22710435/)

[Heckman PR, et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/33192454/)

[Perez-Gonzalez R, et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/30937842/)

[Bura AS, et al, (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/33475283/)

[Menniti FS, et al, (2006) (2006)](https://pubmed.ncbi.nlm.nih.gov/16816838/)

[Conti M, et al, (2003) (2003)](https://pubmed.ncbi.nlm.nih.gov/12574543/)

[Xia J, et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/30602128/)

[Sutphen SA, et al, (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/26315673/)

[Park K, et al, (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/24991833/)

[Kim H, et al, (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29550358/)