Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Target Concepts:
Gene/Protein
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Enzyme
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Query: UMLS:C0014070 (
encephalomyelitis
)
13,017
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Although there is growing evidence for a role of excess intracellular cations, particularly calcium ions, in neuronal and glial cell injury in multiple sclerosis, as well as in non-inflammatory neurological conditions, the molecular mechanisms involved are not fully determined. We previously showed that the
acid-sensing ion channel 1
which, when activated under the acidotic tissue conditions found in inflammatory lesions opens to allow influx of sodium and calcium ions, contributes to axonal injury in experimental autoimmune
encephalomyelitis
, an animal model of multiple sclerosis. However, the extent and cellular distribution of
acid-sensing ion channel 1
expression in neurons and glia in inflammatory lesions is unknown and, crucially,
acid-sensing ion channel 1
expression has not been determined in multiple sclerosis lesions. Here we studied acute and chronic experimental autoimmune
encephalomyelitis
and multiple sclerosis spinal cord and optic nerve tissues to describe in detail the distribution of
acid-sensing ion channel 1
and its relationship with neuronal and glial damage. We also tested the effects of amiloride treatment on tissue damage in the mouse models. We found that
acid-sensing ion channel 1
was upregulated in axons and oligodendrocytes within lesions from mice with acute experimental autoimmune
encephalomyelitis
and from patients with active multiple sclerosis. The expression of
acid-sensing ion channel 1
was associated with axonal damage as indicated by co-localization with the axonal injury marker beta amyloid precursor protein. Moreover, blocking
acid-sensing ion channel 1
with amiloride protected both myelin and neurons from damage in the acute model, and when given either at disease onset or, more clinically relevant, at first relapse, ameliorated disability in mice with chronic-relapsing experimental autoimmune
encephalomyelitis
. Together these findings suggest that blockade of
acid-sensing ion channel 1
has the potential to provide both neuro- and myelo-protective benefits in multiple sclerosis.
...
PMID:Acid-sensing ion channel 1 is involved in both axonal injury and demyelination in multiple sclerosis and its animal model. 2123 44
