[Multiple sclerosis -- a channelopathy? Targeting ion channels and transporters in inflammatory neurodegeneration].
Multiple sclerosis (MS) has traditionally been regarded as an inflammatory demyelinating disorder of the CNS in which clinical symptoms result from axon conduction block caused by myelin degradation. However, typical accumulation of permanent neurological deficits during the clinical course of MS cannot be explained solely by de- and remyelinating processes. It is considered to be rather due to neuronal degeneration, for which several reasons could be identified depending on the state of the disease. First, neurons and their axons can be damaged by infiltrating lymphocytes and macrophages either directly by cell-to-cell contact or by the release of harmful mediators such as nitric oxide or glutamate. Second, indirect injury to neurons and axons may occur through the loss of trophic support by neighbouring oligodendrocytes due to destruction of both the myelin sheath and the oligodendrocyte itself. Third, redistribution of certain voltage- and ligand-gated ion channels and transporters along naked demyelinated axons restores axonal conduction but also leads to excessive spatially restricted electrical activity of the axonal membrane, intracellular calcium accumulation, impairment of mitochondrial function, and subsequent neuronal degeneration. The neuroprotective potential of pharmacological modulation of these channels and transporters using already approved drugs has been demonstrated in several animal studies, is the subject of current clinical trials and will be the topic of this review.
Meuth
S G
SG
Klinik für Neurologie, Klinische Forschungsgruppe für Neuroimmunologie, Julius-Maximilians-Universität, Würzburg, Germany. meuth_s@klinik.uni-wuerzburg.de
Melzer
N
N
Kleinschnitz
C
C
Budde
T
T
Wiendl
H
H
D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism*; D008959:Models, Neurological; D009103:Multiple Sclerosis / Q000503:physiopathology*; D019636:Neurodegenerative Diseases / Q000503:physiopathology*
D007473:Ion Channels