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Trends Mol Med. 2016 May;22(5):377-390. doi: 10.1016/j.molmed.2016.03.008. Epub 2016 Apr 13.

Sodium Channels, Mitochondria, and Axonal Degeneration in Peripheral Neuropathy.

Author information

1
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.
2
Department of Neurology, Maastricht University Medical Center, Maastricht AZ, 6202 The Netherlands.
3
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.

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.

KEYWORDS:

axonal degeneration; bioenergetics; mitochondria; neuropathy; sodium channel

PMID:
27085813
DOI:
10.1016/j.molmed.2016.03.008
[Indexed for MEDLINE]

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