PDE4A — Phosphodiesterase 4A

PDE4A — Phosphodiesterase 4A

Introduction

Pde4A — Phosphodiesterase 4A 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"> [@francis2011]
| Attribute | Value | [@menniti2006]
|-----------|-------| [@perezgonzalez2019]
| Gene Symbol | PDE4A | [@yang2017]
| Full Name | Phosphodiesterase 4A | [@li2011]
| Chromosomal Location | 19p13.2 | [@burgin2010]
| NCBI Gene ID | 5139 | [@richter2013]
| OMIM ID | 180200 | [@heckman2020]
| Ensembl ID | ENSG00000065989 | [@zhang2015]
| UniProt ID | P27815 | [@davis2019]
| Encoded Protein | cAMP-Specific Phosphodiesterase 4A | [@xu2020]
| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Depression, Inflammation |
</div>

Overview

PDE4A encodes a cAMP-specific phosphodiesterase belonging to the PDE4 family. It is one of the most abundant PDEs in the brain and plays critical roles in regulating cAMP signaling in various cell types.

Function

PDE4A specifically hydrolyzes cAMP:

• cAMP → AMP: Catalyzes the breakdown of cAMP toAMP
• cAMP-specific: Does not hydrolyze cGMP
• Isoforms: Multiple splice variants (PDE4A1-11) with different N-termini

Regulation:

• Phosphorylation: PKA phosphorylation can regulate activity
• Protein interactions: Binds to various scaffolding proteins
• Compartmentalization: Targeted to specific cellular compartments

...

PDE4A — Phosphodiesterase 4A

Introduction

Pde4A — Phosphodiesterase 4A 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"> [@francis2011]
| Attribute | Value | [@menniti2006]
|-----------|-------| [@perezgonzalez2019]
| Gene Symbol | PDE4A | [@yang2017]
| Full Name | Phosphodiesterase 4A | [@li2011]
| Chromosomal Location | 19p13.2 | [@burgin2010]
| NCBI Gene ID | 5139 | [@richter2013]
| OMIM ID | 180200 | [@heckman2020]
| Ensembl ID | ENSG00000065989 | [@zhang2015]
| UniProt ID | P27815 | [@davis2019]
| Encoded Protein | cAMP-Specific Phosphodiesterase 4A | [@xu2020]
| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Depression, Inflammation |
</div>

Overview

PDE4A encodes a cAMP-specific phosphodiesterase belonging to the PDE4 family. It is one of the most abundant PDEs in the brain and plays critical roles in regulating cAMP signaling in various cell types.

Function

PDE4A specifically hydrolyzes cAMP:

• cAMP → AMP: Catalyzes the breakdown of cAMP toAMP
• cAMP-specific: Does not hydrolyze cGMP
• Isoforms: Multiple splice variants (PDE4A1-11) with different N-termini

Regulation:

• Phosphorylation: PKA phosphorylation can regulate activity
• Protein interactions: Binds to various scaffolding proteins
• Compartmentalization: Targeted to specific cellular compartments

Key neuronal functions:

• Synaptic plasticity modulation
• Learning and memory
• Mood regulation
• Neurotransmitter signaling
• Neuronal development

Disease Associations

Alzheimer's Disease

• PDE4A activity is increased in AD brains.
• Elevated PDE4A reduces cAMP, impairing memory.
• PDE4 inhibitors improve cognitive function in AD models.
• Anti-inflammatory effects of PDE4 inhibition may benefit AD.

Parkinson's Disease

• PDE4A regulates dopaminergic signaling.
• cAMP dynamics in striatum affected in PD.
• PDE4 inhibition shows neuroprotective potential.

Depression

• PDE4A is a major target of antidepressant drugs.
• Rolipram, a PDE4 inhibitor, has antidepressant effects.
• PDE4 isoforms differently regulate mood-related behaviors.

Expression Pattern

PDE4A is widely expressed:

• High expression: Cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), olfactory bulb, cerebellum
• Moderate expression: Lung, immune cells, heart
• Cellular localization: [Neurons](/entities/neurons), [astrocytes](/entities/astrocytes), [microglia](/entities/microglia), inflammatory cells

Key Publications

Houslay MD, et al. (2005). PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization. Biochem J 388: 357-368. PMID: 15901234(https://pubmed.ncbi.nlm.nih.gov/15901234/)

Menniti FS, et al. (2006). PDE4 as a therapeutic target for CNS disorders. Neuropsychopharmacology 31: 2129-2141. PMID: 16710315(https://pubmed.ncbi.nlm.nih.gov/16710315/)

Zhang HT, et al. (2009). PDE4 inhibition improves learning and memory in aged animals. Neurobiol Aging 30: 849-862. PMID: 17950491(https://pubmed.ncbi.nlm.nih.gov/17950491/)

Background

The study of Pde4A — Phosphodiesterase 4A 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)
• [PDE4A Protein](/proteins/pde4a-protein)
• [cAMP Signaling](/mechanisms/camp-signaling)

External Links

• [NCBI Gene: PDE4A](https://www.ncbi.nlm.nih.gov/gene/5139)
• [UniProt: P27815](https://www.uniprot.org/uniprot/P27815)
• [OMIM: 180200](https://www.omim.org/entry/180200)

References

[Houslay MD, et al, (2005) (2005)](https://pubmed.ncbi.nlm.nih.gov/15853774/)

[Francis SH, et al, (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/20647468/)

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

[Perez-Gonzalez R, et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/30747356/)

[Yang L, et al, (2017) (2017)](https://pubmed.ncbi.nlm.nih.gov/28218679/)

[Li YF, et al, (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/21557946/)

[Burgin AB, et al, (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20163178/)

[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/)

[Zhang HT, et al, (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/25482128/)

[Davis RL, et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/30578942/)

[Xu Y, et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/31260612/)