Bonnie L. Blazer-Yost

Hydrocephalus is caused by an overproduction of cerebrospinal fluid (CSF), an obstruction of fluid movement, or improper reabsorption. CSF accumulation in the brain’s ventricles causes ventriculomegaly, increased intracranial pressure, inflammation, and neural cell injury. Hydrocephalus can arise from brain trauma, hemorrhage, infection, tumors, or genetic mutations. Currently, there is no cure for hydrocephalus. Treatments like shunting and endoscopic third ventriculostomies are used, but, unfortunately, these therapeutic approaches require brain surgery and have high failure rates. The choroid plexus epithelium (CPe) is thought to be the major producer of CSF in the brain. It is a polarized epithelium that regulates ion and water movement from a fenestrated capillary exudate to the ventricles. Despite decades of research, control of electrolyte movement in the CPe is still not fully understood. This review discusses important transporters on the CPe, how some of these are regulated, and which of them could be potential targets for hydrocephalus treatment. To advance the development of hydrocephalus treatments, physiologically relevant preclinical models are crucial. This review covers some of the current animal and cell culture methods used to study hydrocephalus and highlights the need to develop standardized preclinical models that are used by multiple investigators in order to replicate critical findings and resolve controversies regarding potential drug targets.

Over the years, several studies have shown that kinase-regulated signaling pathways are involved in the development of rare genetic diseases. The study of the mechanisms underlying the onset of these diseases has opened a possible way for the development of targeted therapies using particular kinase inhibitors. Some of these are currently used to treat other diseases, such as cancer. This review aims to describe the possibilities of using kinase inhibitors in genetic pathologies such as tuberous sclerosis, RASopathies, and ciliopathies, describing the various pathways involved and the possible targets already identified or currently under study.