Calcium as a Trojan horse in mental diseases-The role of PMCA and PMCA-interacting proteins in bipolar disorder and schizophrenia

Abstract

Although first mentions about calcium disturbances in psychiatric diseases appeared more than 30 years ago, the most recent genomic and proteomic findings confirmed a significant role of Ca²⁺ and Ca²⁺-regulated pathways in development of neuropathological processes, including bipolar disorder and schizophrenia. Moreover, last decades have shown that due to multifactorial nature of both diseases, impairment in neuronal calcium homeostasis may depend not only on disturbed Ca²⁺ entry system, but also on altered extrusion system. A pivotal role in Ca²⁺ clearance mechanism is played by plasma membrane Ca²⁺-ATPase (PMCA), the enzyme responsible for returning the elevated levels of cytosolic Ca²⁺ back to the resting state. In this paper we summarize the current knowledge about the role of PMCA in bipolar disorder and schizophrenia pathologies, as well as the contribution of several proteins that by interaction with PMCA modify signal transduction mechanisms.

Keywords: Bipolar disorder; Calcium pumps; Ketamine; Schizophrenia.