Targeting Carbonic Anhydrase Isozymes in the Treatment of Neurological Disorders

Abstract

Carbonic anhydrases (CAs) are widely expressed in the nervous system where they play important physiological roles. In the brain and other parts of the system, different isozymes show unique distribution patterns, some of them being present in neurons (CA II, V, VII, XIV), capillary endothelium (CA IV), microglia (CA III), choroid plexus (CA II, III, XII, XIV), astrocytes (CA II and V), oligodendrocytes (CA II and XIII), and myelin sheath (CA II). Nervous tissues also express three carbonic anhydrase-related proteins (CARP VIII, X, XI), which may be involved in the brain development processes. Future research is needed to define the exact roles of these highly conserved CA isoforms and to design novel treatment strategies for the diseases caused by defects or abnormal regulation of CARPs. Enzymatically active CA isozymes are known drug targets to treat various neurological disorders including epilepsy, acute mountain sickness, pseudotumor cerebri, and brain edema. In this review article, we describe how the clinically approved CA inhibitors are used for the treatment of these diseases.