Related Experiment Video
Updated: Aug 3, 2025
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Consideration of Kinase Inhibitors for the Treatment of Hydrocephalus
1Biology Department, Indiana University-Purdue University, 723 West Michigan Street, Indianapolis, IN 46202, USA.
Insights
Hydrocephalus treatment lacks long-term pharmaceutical options. Targeting choroid plexus transporters, like TRPV4 and NKCC1, offers a new avenue for drug design to manage cerebrospinal fluid (CSF) production.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Hydrocephalus is characterized by excess cerebrospinal fluid (CSF) accumulation in the brain.
- Current treatments rely on surgical shunt placement, which has high complication rates and requires revision surgeries.
- There are no established long-term pharmaceutical treatments for hydrocephalus.
Purpose of the Study:
- To explore biochemical pathways in hydrocephalus for intelligent drug design.
- To identify potential therapeutic targets for pharmaceutical intervention in hydrocephalus.
Main Methods:
- Investigate the role of fluid-electrolyte homeostasis in hydrocephalus.
- Focus on two key transport proteins in the choroid plexus: transient receptor potential vanilloid 4 (TRPV4) and sodium, potassium, 2 chloride co-transporter 1 (NKCC1).
- Consider kinase regulation of these transporters as potential drug targets.
Main Results:
- TRPV4 and NKCC1 are implicated in CSF production.
- Inhibition or genetic manipulation of these transporters affects CSF volume.
- Kinase inhibitors regulating these transporters are potential therapeutic targets.
Conclusions:
- Understanding choroid plexus transport mechanisms is crucial for hydrocephalus drug development.
- Targeting TRPV4 and NKCC1 presents a promising strategy for novel hydrocephalus therapies.
- Kinase inhibitors offer a potential pharmaceutical approach to manage CSF production in hydrocephalus.
Abstract:
Hydrocephalus is a devastating condition characterized by excess cerebrospinal fluid (CSF) in the brain. Currently, the only effective treatment is surgical intervention, usually involving shunt placement, a procedure prone to malfunction, blockage, and infection that requires additional, often repetitive, surgeries. There are no long-term pharmaceutical treatments for hydrocephalus. To initiate an intelligent drug design, it is necessary to understand the biochemical changes underlying the pathology of this chronic condition. One potential commonality in the various forms of hydrocephalus is an imbalance in fluid-electrolyte homeostasis. The choroid plexus, a complex tissue found in the brain ventricles, is one of the most secretory tissues in the body, producing approximately 500 mL of CSF per day in an adult human. In this manuscript, two key transport proteins of the choroid plexus epithelial cells, transient receptor potential vanilloid 4 and sodium, potassium, 2 chloride co-transporter 1, will be considered. Both appear to play key roles in CSF production, and their inhibition or genetic manipulation has been shown to affect CSF volume. As with most transporters, these proteins are regulated by kinases. Therefore, specific kinase inhibitors are also potential targets for the development of pharmaceuticals to treat hydrocephalus.
Related Concept Videos
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
01:29Venous Thrombosis III: Interprofessional Care
02:34Inhibition of Cdk Activity
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
01:28Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...