Related Experiment Video
Updated: Apr 25, 2026
08:37
Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog
Published on: November 5, 2014
9.3K
Emerging biology of PDE10A
Lindsay S Wilson, Nicholas J Brandon1
1Neuroscience Research Unit, Pfizer Research and Development, Cambridge, MA, USA. Lindsay.S.Wilson@pfizer.com.
Current Pharmaceutical Design
|August 28, 2014
Summary
Cyclic nucleotide phosphodiesterases (PDEs) regulate cell signaling. PDE10A, found in the brain, is a potential target for CNS disorders, prompting a reevaluation of its therapeutic role.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Cyclic AMP (cAMP) and cyclic GMP (cGMP) are crucial second messengers regulating cellular signaling pathways.
- Cyclic nucleotide phosphodiesterases (PDEs) control intracellular levels of cAMP and cGMP by degrading these molecules.
- PDE10A, a specific PDE family, is highly expressed in the brain, particularly in regions relevant to antipsychotic treatment.
Purpose of the Study:
- To review the localization and function of PDE10A in the brain.
- To discuss the role of PDE10A in regulating cAMP and cGMP signaling pathways.
- To explore the therapeutic potential of PDE10A inhibition for CNS disorders, especially those affecting the basal ganglia.
Main Methods:
- Literature review focusing on PDE10A localization and function.
- Analysis of PDE10A's role in intracellular signaling pathways.
- Discussion of PDE10A's relevance to psychiatric and movement disorders.
Main Results:
- PDE10A is uniquely localized within the brain, particularly in the striatum.
- PDE10A activity modulates cAMP and cGMP levels, influencing neuronal function.
- Despite a failed clinical trial for schizophrenia, PDE10A remains a target of interest.
Conclusions:
- PDE10A's specific expression pattern and regulatory role in second messenger signaling make it a significant target for neurological and psychiatric conditions.
- Further investigation into PDE10A's function is warranted for potential therapeutic applications in disorders like bipolar disorder, autism spectrum disorders, Parkinson's disease, and Huntington's disease.
Related Concept Videos
01:58Cell Specific Gene Expression
13.1K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.1K
01:09GPCRs Regulate Adenylyl Cylase Activity
6.8K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.8K
01:27Transducer Mechanism: Enzyme-Linked Receptors
4.4K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
4.4K
02:32Exon Recombination
3.1K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
3.1K
01:34ATP Driven Pumps II: P-type Pumps
5.1K
The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
5.1K
01:10Mechanism of Angiogenesis
6.3K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
6.3K