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A Role for SERCA Pumps in the Neurobiology of Neuropsychiatric and Neurodegenerative Disorders

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Calcium Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1131))

Abstract

Calcium (Ca2+) is a fundamental regulator of cell fate and intracellular Ca2+ homeostasis is crucial for proper function of the nerve cells. Given the complexity of neurons, a constellation of mechanisms finely tunes the intracellular Ca2+ signaling. We are focusing on the sarco/endoplasmic reticulum (SR/ER) calcium (Ca2+)-ATPase (SERCA) pump, an integral ER protein. SERCA’s well established role is to preserve low cytosolic Ca2+ levels ([Ca2+]cyt), by pumping free Ca2+ ions into the ER lumen, utilizing ATP hydrolysis. The SERCA pumps are encoded by three distinct genes, SERCA1-3, resulting in 12 known protein isoforms, with tissue-dependent expression patterns. Despite the well-established structure and function of the SERCA pumps, their role in the central nervous system is not clear yet. Interestingly, SERCA-mediated Ca2+ dyshomeostasis has been associated with neuropathological conditions, such as bipolar disorder, schizophrenia, Parkinson’s disease and Alzheimer’s disease. We summarize here current evidence suggesting a role for SERCA in the neurobiology of neuropsychiatric and neurodegenerative disorders, thus highlighting the importance of this pump in brain physiology and pathophysiology.

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Acknowledgements

A.B. was supported by the University of Dayton (UD) Graduate School and by the UD Office for Graduate Affairs through the Graduate Student Summer Fellowship (GSSF) Program. J.S. was supported by a Barry Goldwater Scholarship in Excellence and Education Award, a Biology Department Lancaster-McDougall Award, a CAS Dean Fellowship, the Berry Summer Thesis Institute, and the UD Honors Program. P.M.P. was supported by an inaugural STEM Catalyst grant and Start-up funding from UD, as well as by Research Council Seed Grants (RCSG) from the University of Dayton Research Institute (UDRI); this work was supported by the National Institute Of Neurological Disorders and Stroke of the National Institutes of Health under award number R03NS109836 (to P.M.P.). Funding sponsors had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Conflict of Interest None.

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Britzolaki, A., Saurine, J., Klocke, B., Pitychoutis, P.M. (2020). A Role for SERCA Pumps in the Neurobiology of Neuropsychiatric and Neurodegenerative Disorders. In: Islam, M. (eds) Calcium Signaling. Advances in Experimental Medicine and Biology, vol 1131. Springer, Cham. https://doi.org/10.1007/978-3-030-12457-1_6

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