Pde1C — 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-gene"> [@soderling2001]
<table> [@pde2010]
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Phosphodiesterase 1C</th></tr> [@amyloidbeta2009]
<tr><td><strong>Gene Symbol</strong></td><td>PDE1C</td></tr> [@pde2013]
<tr><td><strong>Full Name</strong></td><td>Phosphodiesterase 1C</td></tr> [@calciumcalmodulin2000]
<tr><td><strong>Chromosome</strong></td><td>2p21</td></tr> [@pde2015]
<tr><td><strong>NCBI Gene ID</strong></td><td>[5156](https://www.ncbi.nlm.nih.gov/gene/5156)</td></tr> [@pdec2009]
<tr><td><strong>OMIM</strong></td><td>618033</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000154678</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q14139](https://www.uniprot.org/uniprot/Q14139)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Cancer</td></tr>
</table>
</div>
Pde1C — 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-gene"> [@soderling2001]
<table> [@pde2010]
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Phosphodiesterase 1C</th></tr> [@amyloidbeta2009]
<tr><td><strong>Gene Symbol</strong></td><td>PDE1C</td></tr> [@pde2013]
<tr><td><strong>Full Name</strong></td><td>Phosphodiesterase 1C</td></tr> [@calciumcalmodulin2000]
<tr><td><strong>Chromosome</strong></td><td>2p21</td></tr> [@pde2015]
<tr><td><strong>NCBI Gene ID</strong></td><td>[5156](https://www.ncbi.nlm.nih.gov/gene/5156)</td></tr> [@pdec2009]
<tr><td><strong>OMIM</strong></td><td>618033</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000154678</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q14139](https://www.uniprot.org/uniprot/Q14139)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Cancer</td></tr>
</table>
</div>
PDE1C (Phosphodiesterase 1C) is a calcium/calmodulin-dependent phosphodiesterase that hydrolyzes both [cAMP](/entities/cyclic-amp) and [cGMP](/entities/cyclic-gmp), serving as a critical regulator of cyclic nucleotide signaling in cells. The gene is located on chromosome 2p21 and encodes a protein of approximately 87 kDa. PDE1C is highly expressed in the [brain](/brain-regions/brain-overview), particularly in the [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and [cerebellum](/brain-regions/cerebellum), where it plays essential roles in [synaptic plasticity](/mechanisms/synaptic-plasticity), memory formation, and neuronal survival.
PDE1C is unique among the PDE family in its dual-substrate specificity and strong brain expression, making it a key link between [calcium signaling](/mechanisms/calcium-signaling-neurodegeneration) and cyclic nucleotide pathways. This positioning as a signaling integrator has made PDE1C a focal point for understanding neurodegenerative disease mechanisms and developing therapeutic interventions.
The PDE1C gene spans approximately 41 kb and contains 26 exons. Multiple transcription initiation sites generate alternatively spliced variants with distinct tissue distribution patterns. The promoter region contains response elements for several transcription factors, including CREB (cAMP Response Element-Binding Protein), allowing activity-dependent regulation.
PDE1C exhibits a distinctive expression pattern:
In [neurons](/cell-types/neurons), PDE1C localizes to both dendritic and somatic compartments, where it regulates:
The PDE1C protein contains several distinct functional domains:
PDE1C catalyzes the hydrolysis of:
PDE1C provides a critical link between [calcium signaling](/mechanisms/calcium-signaling-neurodegeneration) and cyclic nucleotide pathways:
PDE1C plays a crucial role in [synaptic plasticity](/mechanisms/synaptic-plasticity):
PDE1C activity influences neuronal survival through:
PDE1C has significant implications for [Alzheimer's disease](/diseases/alzheimers-disease) pathogenesis:
| Aspect | Mechanism | Evidence |
|--------|-----------|----------|
| Memory impairment | Elevated PDE1C activity reduces cAMP, impairing synaptic plasticity | Preclinical studies show PDE1 inhibition improves memory |
| [Amyloid-beta](/proteins/amyloid-beta) pathology | Aβ oligomers dysregulate PDE1C-cAMP signaling | Reduced PDE1C activity in AD brain |
| [Tau](/proteins/tau) pathology | cAMP/PKA signaling affects tau phosphorylation | PDE1 inhibitors reduce tau pathology in models |
| Therapeutic potential | PDE1 inhibitors enhance cognitive function | Clinical trials ongoing |
Key mechanisms include:
In [Parkinson's disease](/diseases/parkinsons-disease), PDE1C affects:
PDE1C alterations in [Huntington's disease](/diseases/huntington-disease):
In [ALS](/diseases/amyotrophic-lateral-sclerosis):
Several PDE1 inhibitors have been developed for neurological applications:
| Inhibitor | Selectivity | Development Status | Notes |
|-----------|-------------|-------------------|-------|
| Vinpocetine | PDE1 | Approved (cognitive supplement) | Mild PDE1 inhibition |
| IC86340 | PDE1 | Preclinical | Selective for PDE1C |
| KR-36996 | PDE1 | Preclinical | Neuroprotective effects |
| PF-04447943 | PDE1A | Clinical trials | Tested in AD |
PDE1C inhibition is being explored for:
PDE1C interacts with multiple signaling pathways:
PDE1C forms complexes with:
Pde1c knockout mice show:
Mouse models overexpressing PDE1C exhibit:
PDE1C polymorphisms have been associated with:
PDE1C expression/activity may serve as:
Current research focuses on:
The study of Pde1C — 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.