Abstract
In this issue of Molecular Pharmacology (p. 665), Pannacione et al. provide evidence of a role for the voltage-gated potassium channel alpha subunit Kv3.4 and its ancillary subunit MiRP2 in beta-amyloid (Abeta) peptide-mediated neuronal death. The MiRP2-Kv3.4 channel complex-previously found to be important in skeletal myocyte physiology-is now argued to be a molecular correlate of the transient outward potassium current up-regulated by Abeta peptide, considered a significant step in the etiology of Alzheimer's disease. The authors conclude that MiRP2 and Kv3.4 are up-regulated by Abeta peptide in a nuclear factor kappaB-dependent fashion at the transcriptional level, and the sea anemone toxin BDS-I is shown to protect against Abeta peptide-mediated cell death by specific blockade of Kv3.4-generated current. The findings lend weight to the premise that specific channels, such as MiRP2-Kv3.4, could hold promise as future therapeutic targets in Alzheimer's disease and potentially other neurodegenerative disorders.
Publication types
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Comment
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Research Support, N.I.H., Extramural
MeSH terms
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Alzheimer Disease / etiology
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Alzheimer Disease / genetics*
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Alzheimer Disease / metabolism*
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Alzheimer Disease / pathology
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Amyloid beta-Peptides / chemistry
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Amyloid beta-Peptides / toxicity
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Animals
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Apoptosis / drug effects
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Cell Death / drug effects
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Cnidarian Venoms / pharmacology
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Humans
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Models, Biological
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Muscle, Skeletal / chemistry
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Muscle, Skeletal / cytology
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Muscle, Skeletal / metabolism*
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NF-kappa B / antagonists & inhibitors
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Peptide Fragments / chemistry
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Peptide Fragments / toxicity
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Potassium Channel Blockers / pharmacology
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Potassium Channels, Voltage-Gated / antagonists & inhibitors
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Potassium Channels, Voltage-Gated / physiology*
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Sea Anemones / chemistry
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Shaw Potassium Channels / antagonists & inhibitors
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Shaw Potassium Channels / physiology*
Substances
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Amyloid beta-Peptides
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BDS-I antiviral protein, Anemonia sulcata
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Cnidarian Venoms
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KCNE3 protein, human
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NF-kappa B
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Peptide Fragments
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Potassium Channel Blockers
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Potassium Channels, Voltage-Gated
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Shaw Potassium Channels
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amyloid beta-protein (1-42)