Mitotoxicity in distal symmetrical sensory peripheral neuropathies.
Mitotoxicity in distal symmetrical sensory peripheral neuropathies.
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DOI：
10.1038/nrneurol.2014.77
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发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Salvemini D
中科院分区：
文献类型：
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作者：
Bennett GJ;Doyle T;Salvemini D
慢性远端对称性感觉周围神经病变是癌症化疗、HIV治疗和糖尿病的常见神经系统并发症。虽然病因特异性的表现差异是明显的，但这些神经病的临床体征和症状明显相似。来自神经性疼痛动物模型的数据表明，相似性有一个共同的原因：初级传入感觉神经元的线粒体功能障碍。线粒体功能障碍是由几种化学类别的癌症化疗药物、HIV相关病毒蛋白和核苷逆转录酶抑制剂治疗的线粒体毒性作用以及过量葡萄糖的（可能直接和间接）作用引起的。线粒体损伤导致慢性神经元能量不足，这引起自发神经冲动和房室神经元变性，这首先在皮肤传入神经元的末端受体树枝中明显，即表皮内神经鞘。初步数据表明，预防线粒体损伤或改善线粒体功能的药物可能有助于治疗这些疾病。
Chronic distal symmetrical sensory peripheral neuropathy is a common neurological complication of cancer chemotherapy, HIV treatment and diabetes. Although aetiology-specific differences in presentation are evident, the clinical signs and symptoms of these neuropathies are clearly similar. Data from animal models of neuropathic pain suggest that the similarities have a common cause: mitochondrial dysfunction in primary afferent sensory neurons. Mitochondrial dysfunction is caused by mitotoxic effects of cancer chemotherapeutic drugs of several chemical classes, HIV-associated viral proteins, and nucleoside reverse transcriptase inhibitor treatment, as well as the (possibly both direct and indirect) effects of excess glucose. The mitochondrial injury results in a chronic neuronal energy deficit, which gives rise to spontaneous nerve impulses and a compartmental neuronal degeneration that is first apparent in the terminal receptor arbor—that is, intraepidermal nerve fibres—of cutaneous afferent neurons. Preliminary data suggest that drugs that prevent mitochondrial injury or improve mitochondrial function could be useful in the treatment of these conditions.