A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels
Articolo
Data di Pubblicazione:
2016
Citazione:
A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels / H. Rolyan, S. Liu, J. Gj Hoeijmakers, C.G. Faber, I. Sj Merkies, G. LAURIA PINTER, J.A. Black, S.G. Waxman. - In: MOLECULAR PAIN. - ISSN 1744-8069. - 12:(2016 Nov 07). [10.1177/1744806916674472]
Abstract:
Small fiber neuropathy is a painful sensory nervous system disorder characterized by damage to unmyelinated C- and thinly
myelinated Ad- nerve fibers, clinically manifested by burning pain in the distal extremities and dysautonomia. The clinical
onset in adulthood suggests a time-dependent process. The mechanisms that underlie nerve fiber injury in small fiber
neuropathy are incompletely understood, although roles for energetic stress have been suggested. In the present study,
we report time-dependent degeneration of neurites from dorsal root ganglia neurons in culture expressing small fiber
neuropathy-associated G856D mutant Nav1.7 channels and demonstrate a time-dependent increase in intracellular calcium
levels [Ca2þ]i and reactive oxygen species, together with a decrease in ATP levels. Together with a previous clinical report of
burning pain in the feet and hands associated with reduced levels of Naþ/Kþ-ATPase in humans with high altitude sickness,
the present results link energetic stress and reactive oxygen species production with the development of a painful neuropathy
that preferentially affects small-diameter axons.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
ATP, axon degeneration, mitochondria, peripheral neuropathy, reactive oxygen species, sodium-calcium exchanger, voltagegated
sodium channe
Elenco autori:
H. Rolyan, S. Liu, J. Gj Hoeijmakers, C.G. Faber, I. Sj Merkies, G. LAURIA PINTER, J.A. Black, S.G. Waxman
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