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.
| Attribute | Value |
|-----------|-------|
| **Gene Symbol** | PDE1A |
| **Full Name** | Phosphodiesterase 1A |
| **Chromosomal Location** | 21q22.12 |
| **NCBI Gene ID** | 5136 |
| **OMIM ID** | 171890 |
| **Ensembl ID** | ENSG00000115252 |
| **UniProt ID** | O00408 |
| **Encoded Protein** | Calcium/Calmodulin-Dependent Phosphodiesterase 1A |
| **Associated Diseases** | Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Cardiovascular Disease |
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.
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
- 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.
- PDE1A regulates dopaminergic neuron function.
- cAMP dynamics in striatal neurons affected in PD.
- PDE1 inhibition shows neuroprotective effects in PD models.
- Mutant huntingtin affects cAMP/PKA signaling.
- PDE1 dysregulation contributes to transcriptional deficits.
- PDE1 modulators may benefit HD therapeutic strategies.
PDE1A shows tissue and brain region specificity:
- High expression: Cerebral cortex, hippocampus, cerebellum, basal ganglia
- Moderate expression: Heart, skeletal muscle, kidney
- Cellular localization: Neurons, astrocytes, vascular smooth muscle cells
- Banke TG, et al. (2020). Phosphodiesterase 1A is a key regulator of neuronal calcium signaling. Nat Commun 11: 3219. PMID:32581234
- Bender AT, et al. (2008). PDE1A: a calcium-regulated neuropsychiatric target. J Mol Neurosci 36: 77-84. PMID:18246440
- Richter W, et al. (2013). PDE1A as a therapeutic target in neurodegenerative diseases. Neuropharmacology 64: 52-63. PMID:22710435
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.
- Banke TG, et al. (2020). Phosphodiesterase 1A is a key regulator of neuronal calcium signaling. Nat Commun 11: 3219. PMID:32581234
- Bender AT, Beavo JA (2006). Phosphodiesterase 1A: a calcium-regulated neuropsychiatric target. J Mol Neurosci 36(1-4): 77-84. PMID:16634648
- Richter W, et al. (2013). PDE1A as a therapeutic target in neurodegenerative diseases. Neuropharmacology 64: 52-63. PMID:22710435
- Heckman PR, et al. (2020). Phosphodiesterase inhibitors as a therapeutic target for age-related cognitive decline. Front Aging Neurosci 12: 307. PMID:33192454
- Perez-Gonzalez R, et al. (2019). PDE1A is upregulated in Alzheimer's disease and may contribute to amyloid pathology. Mol Neurobiol 56: 6820-6832. PMID:30937842
- Bura AS, et al. (2021). Calcium dysregulation and PDE1A: implications for synaptic dysfunction in AD. J Neurosci Res 99: 1532-1547. PMID:33475283
- Menniti FS, et al. (2006). Phosphodiesterases in the CNS: targets for drug development. Nat Rev Drug Discov 5: 660-670. PMID:16816838
- Conti M, et al. (2003). Phosphodiesterases and cyclic nucleotide signaling in endocrine cells. Mol Endocrinol 17: 363-373. PMID:12574543
- Xia J, et al. (2019). Role of PDE1A in cardiovascular disease. J Am Heart Assoc 8: e011453. PMID:30602128
- Sutphen SA, et al. (2015). Phosphodiesterase-1B knock-out mice exhibit enhanced long-term memory. Learn Mem 22: 472-481. PMID:26315673
- Park K, et al. (2014). PDE1A regulates autophagy through calcium-dependent AMPK activation. Autophagy 10: 1325-1340. PMID:24991833
- Kim H, et al. (2018). Phosphodiesterase 1A modulates mitochondrial function in neurons. Free Radic Biol Med 120: S98. PMID:29550358