Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes which use CO₂ as substrate, catalysing its interconversion to bicarbonate and a proton. In humans 15 CAs are expressed, 12 of which are catalytically active: the cytosolic CA I-III, VII, XIII, the membrane-bound CA IV, the mitochondrial CA VA and VB, the secreted CA VI, and the transmembrane CA IX, XII, XIV. Nine isoforms are present in the mammalian brain. Evidence supporting that CA inhibitors impair memory in humans has come from studies on topiramate and acetazolamide during acute high-altitude exposure. In contrast, administration of CA activators in animal models enhances memory and learning. Here we review the involvement of selective CA inhibition/activation in cognition-related disorders. CAs may represent a crucial family of new targets for improving cognition as well as in therapeutic areas, such as phobias, obsessive-compulsive disorder, generalised anxiety, and post-traumatic stress disorders, for which few efficient therapies are available.

摘要

碳酸酐酶（CAs，EC 4.2.1.1）是使用CO _2的金属酶作为底物，催化其相互转化为碳酸氢根和质子。在人类中表达了15种CA，其中12种具有催化活性：胞质CA I-III，VII，XIII，膜结合CA IV，线粒体CA VA和VB，分泌的CA VI和跨膜CA IX，十二，十四 哺乳动物脑中存在九种亚型。关于CA抑制剂损害人类记忆力的证据来自对急性高空暴露期间托吡酯和乙酰唑胺的研究。相反，在动物模型中施用CA激活剂可增强记忆力和学习能力。在这里，我们回顾了选择性CA抑制/激活与认知相关疾病的参与。CA可能代表着重要的新目标家族，可用于提高认知度以及在诸如恐惧症，强迫症，