Sodium Channels, Mitochondria, and Axonal Degeneration in Peripheral Neuropathy

详细信息    查看全文

• 作者：Anna-Karin Persson¹ ; ² ; Janneke G.J. Hoeijmakers³ ; Mark Estacion¹ ; ² ; Joel A. Black¹ ; ² ; Stephen G. Waxman¹ ; ² ; ^{stephen.waxman@yale.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：axonal degeneration ; bioenergetics ; mitochondria ; neuropathy ; sodium channel
• 刊名：Trends in Molecular Medicine
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：22
• 期：5
• 页码：377-390
• 全文大小：3004 K

文摘

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⁺/Ca²⁺ 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.