title: Mechanisms of neuronal damage in multiple sclerosis and its animal models: role of calcium pumps and exchangers.
abstract: Multiple sclerosis is an inflammatory, demyelinating and neurodegenerative disorder of the central nervous system. Increasing evidence indicates that neuronal pathology and axonal injury are early hallmarks of multiple sclerosis and are major contributors to progressive and permanent disability. Yet, the mechanisms underlying neuronal dysfunction and damage are not well defined. Elucidation of such mechanisms is of critical importance for the development of therapeutic strategies that will prevent neurodegeneration and confer neuroprotection. PMCA2 (plasma-membrane Ca(2+)-ATPase 2) and the NCX (Na(+)/Ca(2+) exchanger) have been implicated in impairment of axonal and neuronal function in multiple sclerosis and its animal models. As PMCA2 and NCX play critical roles in calcium extrusion in cells, alterations in their expression or activity may affect calcium homoeostasis and thereby induce intracellular injury mechanisms. Interventions that restore normal PMCA2 and NCX activity may prevent or slow disease progression by averting neurodegeneration.
authors.affiliation: Department of Neurology and Neuroscience, MSB, H-506, New Jersey Medical School, UMDNJ (University of Medicine and Dentistry of New Jersey), 185 South Orange Ave., Newark, NJ 07103, U.S.A.
authors.forename: M P
authors.initials: MP
authors.lastname: Kurnellas
authors.forename: K C
authors.initials: KC
authors.lastname: Donahue
authors.forename: S
authors.initials: S
authors.lastname: Elkabes
mesh_terms: D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D004195:Disease Models, Animal; D009103:Multiple Sclerosis / Q000473:pathology*; D009474:Neurons / Q000473:pathology*
chemical_list: D000252:Calcium-Transporting ATPases