Biology Department, Indiana University-Purdue University, 723 West Michigan Street, Indianapolis, IN 46202, USA.
Int J Mol Sci. 2023 Apr 3;24(7):6673. doi: 10.3390/ijms24076673.
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.
脑积水是一种破坏性疾病，其特征是大脑中有过多的脑脊液（CSF）。目前，唯一有效的治疗方法是手术干预，通常涉及分流器的放置，但该手术容易发生故障、堵塞和感染，需要额外的、通常是重复的手术。目前没有针对脑积水的长期药物治疗。要进行智能药物设计，就必须了解这种慢性疾病病理背后的生化变化。各种类型的脑积水的一个潜在共同点是液体-电解质稳态失衡。脉络丛是一种位于脑室内的复杂组织，是人体中最具分泌功能的组织之一，在成年人中每天可产生约 500 毫升的 CSF。在本文中，将考虑脉络丛上皮细胞的两个关键转运蛋白，即瞬时受体电位香草素 4 和钠钾 2 氯协同转运蛋白 1。这两种蛋白似乎都在 CSF 产生中发挥关键作用，其抑制或基因操作已被证明会影响 CSF 量。与大多数转运蛋白一样，这些蛋白受激酶调节。因此，特定的激酶抑制剂也是开发治疗脑积水药物的潜在靶点。
