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Role of plasma membrane calcium ATPase 2 in spinal cord pathology

Author(s): Amanda Kathleen Fakira | Stella Elkabes

Journal: World Journal of Biological Chemistry
ISSN 1949-8454

Volume: 1;
Issue: 5;
Start page: 103;
Date: 2010;
Original page

Keywords: Multiple sclerosis | Spinal cord injury | Neuroprotection | Neurodegeneration | Excitotoxicity | ATP2b2 | Calpain | Glia

A number of studies have indicated that plasma membrane calcium ATPases (PMCAs) are expressed in the brain and spinal cord and could play important roles not only in the maintenance of cellular calcium homeostasis but also in the survival and function of central nervous system cells under pathological conditions. The different regional and cellular distributions of the various PMCA isoforms and splice variants in the nervous system and the diverse phenotypes of PMCA knockout mice support the notion that each isoform might play a distinct role. Especially in the spinal cord, the survival of neurons and, in particular, motor neurons could be dependent on PMCA2. This is indicated by the knockdown of PMCA2 in pure spinal cord neuronal cultures that leads to cell death via a decrease in collapsing response mediator protein 1 levels. Moreover, the progressive decline in the number of motor neurons in PMCA2-null mice and heterozygous mice further supports this notion. Therefore, the reported reduction in PMCA2 mRNA and protein levels in the inflamed spinal cord of mice affected by experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, and after spinal cord contusion injury, suggests that changes in PMCA2 expression could be a cause of neuronal pathology and death during inflammation and injury. Glutamate excitotoxicity mediated via kainate receptors has been implicated in the neuropathology of both EAE and spinal cord injury, and has been identified as a trigger that reduces PMCA2 levels in pure spinal cord neuronal cultures through degradation of the pump by calpain without affecting PMCA2 transcript levels. It remains to be determined which other stimuli modulate PMCA2 mRNA expression in the aforementioned pathological conditions of the spinal cord.
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