Mechanisms of neuronal damage in multiple sclerosis and its animal models: Role of calcium pumps and exchangers

TY - JOUR

T1 - Mechanisms of neuronal damage in multiple sclerosis and its animal models

T2 - Role of calcium pumps and exchangers

AU - Kurnellas, M. P.

AU - Donahue, K. C.

AU - Elkabes, S.

PY - 2007/11

Y1 - 2007/11

N2 - 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 Ca2+-ATPase 2) and the NCX (Na+/Ca2+ 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.

AB - 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 Ca2+-ATPase 2) and the NCX (Na+/Ca2+ 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.

KW - Calcium dyshomoeostasis

KW - Experimental autoimmune encephalomyelitis

KW - Multiple sclerosis

KW - Neurodegeneration

KW - Plasma-membrane Ca-ATPase (PMCA)

UR - http://www.scopus.com/inward/record.url?scp=36749082529&partnerID=8YFLogxK

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U2 - 10.1042/BST0350923

DO - 10.1042/BST0350923

M3 - Article

C2 - 17956247

SN - 0300-5127

VL - 35

SP - 923

EP - 926

JO - Biochemical Society transactions

JF - Biochemical Society transactions

IS - 5

ER -