PDE1C Protein — Phosphodiesterase 1C

title: PDE1C Protein — Phosphodiesterase 1C
category: protein

Phosphodiesterase 1C (PDE1C)

Introduction

Pde1C Protein — Phosphodiesterase 1C 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">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Phosphodiesterase 1C</th></tr>
<tr><td><strong>Protein Name</strong></td><td>PDE1C</td></tr>
<tr><td><strong>Gene</strong></td><td>[PDE1C](/genes/pde1c)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q14139](https://www.uniprot.org/uniprot/Q14139)</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>6X4O, 5JOX</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>87 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cytoplasm, membrane-associated</td></tr>
<tr><td><strong>Brain Expression</strong></td><td>Widespread in [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

...

title: PDE1C Protein — Phosphodiesterase 1C
category: protein

Phosphodiesterase 1C (PDE1C)

Introduction

Pde1C Protein — Phosphodiesterase 1C 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">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Phosphodiesterase 1C</th></tr>
<tr><td><strong>Protein Name</strong></td><td>PDE1C</td></tr>
<tr><td><strong>Gene</strong></td><td>[PDE1C](/genes/pde1c)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q14139](https://www.uniprot.org/uniprot/Q14139)</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>6X4O, 5JOX</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>87 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cytoplasm, membrane-associated</td></tr>
<tr><td><strong>Brain Expression</strong></td><td>Widespread in [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

PDE1C (Phosphodiesterase 1C, encoded by the [PDE1C](/genes/pde1c) gene) is a calcium/calmodulin-dependent phosphodiesterase that hydrolyzes both cAMP and cGMP. It is one of the most abundant phosphodiesterases in the [brain](/brain-regions/brain-overview) and plays crucial roles in [synaptic plasticity](/mechanisms/synaptic-plasticity), memory formation, and neuronal survival.

PDE1C provides a critical link between [calcium signaling](/mechanisms/calcium-signaling-neurodegeneration) and cyclic nucleotide pathways, making it a key regulator of neuronal function and a potential therapeutic target for [neurodegenerative diseases](/diseases/neurodegeneration).

Structure

PDE1C contains several functional domains:

• N-terminal regulatory domain: Contains calmodulin-binding motifs
• EF-hand motifs: Two calcium-binding motifs for calmodulin activation
• C-terminal catalytic domain: Contains PDE signature motifs for hydrolysis
• Dimerization interface: Enables formation of functional dimers

Function

Cyclic Nucleotide Hydrolysis

PDE1C hydrolyzes:

• [cAMP](/entities/cyclic-amp): Second messenger critical for [synaptic plasticity](/mechanisms/synaptic-plasticity) and memory
• [cGMP](/entities/cyclic-gmp): Involved in [nitric oxide signaling](/mechanisms/nitric-oxide-signaling) and neuroprotection

Calcium-Calmodulin Regulation

• Activated by calcium/calmodulin complex
• Provides link between calcium signaling and cAMP/cGMP regulation
• Allows integration of multiple signaling pathways in [neurons](/cell-types/neurons)

Brain Functions

• Synaptic plasticity: Modulates cAMP/cGMP levels at [synapses](/brain-regions/synapse-structure)
• Memory formation: Critical for [hippocampal](/brain-regions/hippocampus)-dependent learning
• Neuronal excitability: Regulates ion channel function through cyclic nucleotides

Role in Neurodegenerative Diseases

Alzheimer's Disease

PDE1C involvement in [Alzheimer's disease](/diseases/alzheimers-disease):

• Memory impairment: PDE1C inhibition improves memory in AD models[@pde]
• [Amyloid-beta](/proteins/amyloid-beta) effects: [Amyloid-beta](/proteins/amyloid-beta-protein) reduces PDE1C activity, disrupting cAMP signaling[@amyloidbeta]
• Therapeutic potential: PDE1 inhibitors show promise in AD preclinical studies

Parkinson's Disease

In [Parkinson's disease](/diseases/parkinsons-disease):

• Dopaminergic signaling: PDE1C regulates cAMP in [dopaminergic neurons](/cell-types/dopaminergic-neurons)[@pdea]
• Neuroprotection: PDE1 inhibition protects against MPTP toxicity
• Levodopa response: May modulate response to dopaminergic therapy

Huntington's Disease

In [Huntington's disease](/diseases/huntington-disease):

• cAMP signaling: PDE1C alterations affect mutant [huntingtin](/proteins/huntingtin) function
• Therapeutic targeting: PDE1 inhibitors under investigation

Amyotrophic Lateral Sclerosis (ALS)

In [ALS](/diseases/amyotrophic-lateral-sclerosis):

• Motor neuron survival: cAMP dysregulation contributes to [motor neuron degeneration](/cell-types/motor-neurons)
• Glial involvement: PDE1C in [astrocytes](/cell-types/astrocytes) affects neuronal support

Therapeutic Targeting

PDE1C is a promising drug target for neurodegenerative diseases:

Inhibitors

• Vinpocetine: Traditional PDE1 inhibitor, studied for cognitive enhancement
• IC86340: Selective PDE1 inhibitor
• KR-36996: Potent PDE1 inhibitor with neuroprotective effects

Clinical Applications

• Cognitive enhancement in aging and dementia
• Neuroprotection in Parkinson's disease
• Adjunct therapy in depression and ADHD

Interactions and Signaling Pathways

PDE1C interacts with:

• Calmodulin (activation)
• cAMP-dependent protein kinase (PKA)
• cGMP-dependent protein kinase (PKG)
• CREB transcription factor
• Various ion channels

Background

The study of Pde1C Protein — Phosphodiesterase 1C 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

• Gene: PDE1C
• [Diseases: Alzheimer's Disease](/content/diseases)
• [Diseases: Parkinson's Disease](/content/diseases)
• [Diseases: Huntington's Disease](/content/diseases)
• [Mechanisms: Synaptic Plasticity](/content/mechanisms)
• [Mechanisms: Calcium Signaling in Neurodegeneration](/content/mechanisms)
• Molecules: cAMP
• Molecules: cGMP

External Links

• [UniProt: PDE1C (Q14139)](https://www.uniprot.org/uniprot/Q14139)
• [PDB: PDE1C Structures (6X4O, 5JOX)](https://www.ebi.ac.uk/pdbe/)
• [Human Protein Atlas: PDE1C](https://www.proteinatlas.org/ENSG00000154640-PDE1C)

References

[Unknown, PDE1 inhibition improves memory in Alzheimer's disease models (PMID:20452377) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/20452377/))

[Unknown, Amyloid-beta effects on phosphodiesterase signaling (PMID:19158546) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/19158546/))

[Unknown, PDE1 in dopaminergic neuron function and Parkinson's disease (PMID:23474447) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/23474447/))

[Unknown, Calcium-calmodulin phosphodiesterases in the brain (PMID:10517883) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/10517883/))

[Unknown, PDE1 inhibitors as therapeutic agents for neurodegenerative diseases (PMID:25880023) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/25880023/))