title: Sodium Channels, Mitochondria, and Axonal Degeneration in Peripheral Neuropathy.
abstract: Peripheral neuropathy results from damage to peripheral nerves and is often accompanied by pain in affected limbs. Treatment represents an unmet medical need and a thorough understanding of the mechanisms underlying axonal injury is needed. Longer nerve fibers tend to degenerate first (length-dependence), and patients carrying pathogenic mutations throughout life usually become symptomatic in mid- or late-life (time-dependence). The activity of voltage-gated sodium channels can contribute to axonal injury and sodium channel gain-of-function mutations have been linked to peripheral neuropathy. Recent studies have implicated sodium channel activity, mitochondrial compromise, and reverse-mode Na(+)/Ca(2+) exchange in time- and length-dependent axonal injury. Elucidation of molecular mechanisms underlying axonal injury in peripheral neuropathy may provide new therapeutic strategies for this painful and debilitating condition.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Persson
authors.affiliation: Department of Neurology, Maastricht University Medical Center, Maastricht AZ, 6202 The Netherlands.
authors.forename: Janneke G J
authors.initials: JGJ
authors.lastname: Hoeijmakers
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Estacion
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Black
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA. Electronic address: stephen.waxman@yale.edu.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D009410:Nerve Degeneration; D010146:Pain / Q000209:etiology; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D015222:Sodium Channels
keywords: axonal degeneration; bioenergetics; mitochondria; neuropathy; sodium channel