The SERCA2: A Gatekeeper of Neuronal Calcium Homeostasis in the Brain
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Calcium (Ca2+) ions are prominent cell signaling regulators that carry information for a variety of cellular processes and are critical for neuronal survival and function. Furthermore, Ca2+ acts as a prominent second messenger that modulates divergent intracellular cascades in the nerve cells. Therefore, nerve cells have developed intricate Ca2+ signaling pathways to couple the Ca2+ signal to their biochemical machinery. Notably, intracellular Ca2+ homeostasis greatly relies on the rapid redistribution of Ca2+ ions into the diverse subcellular organelles which serve as Ca2+ stores, including the endoplasmic reticulum (ER). It is well established that Ca2+ released into the neuronal cytoplasm is pumped back into the ER by the sarco-/ER Ca2+ ATPase 2 (SERCA2), a P-type ion-motive ATPase that resides on the ER membrane. Even though the SERCA2 is constitutively expressed in nerve cells, its precise role in brain physiology and pathophysiology is not well-characterized. Intriguingly, SERCA2-dependent Ca2+ dysregulation has been implicated in several disorders that affect cognitive function, including Darier’s disease, schizophrenia, Alzheimer’s disease, and cerebral ischemia. The current review summarizes knowledge on the expression pattern of the different SERCA2 isoforms in the nervous system, and further discusses evidence of SERCA2 dysregulation in various neuropsychiatric disorders. To the best of our knowledge, this is the first literature review that specifically highlights the critical role of the SERCA2 in the brain. Advancing knowledge on the role of SERCA2 in maintaining neuronal Ca2+ homeostasis may ultimately lead to the development of safer and more effective pharmacotherapies to combat debilitating neuropsychiatric disorders.
KeywordsCalcium SERCA2 Brain Neuron Darier’s disease
AB and CT were 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. JS was supported by the Berry Summer Thesis Institute, the UD Honors Program, and by UD’s STEM Catalyst Grant program. EF was supported by a Biology Department Lancaster-McDougall Award, a Stander Undergraduate Research Fellowship, and a CAS Dean’s Summer Research fellowship. PMP was supported by an inaugural STEM Catalyst grant from the University of Dayton, as well as by Research Council Seed Grants (RCSG) from the University of Dayton Research Institute (UDRI). This review paper was compiled in the context of our “Neuropharmacology” (BIO496/596; Fall 2017) course at the University of Dayton. 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.
AB and JS conducted the primary literature search and wrote the manuscript. EF and CT contributed to the final version of the manuscript. PMP formulated the concept, supervised the literature search and reviewed the manuscript.
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Conflict of interest
The authors declare that they have no conflict of interest.
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