Department of Neurology, University of Michigan, Ann Arbor, MI, United States.
Department of Neurology, University of Michigan, Ann Arbor, MI, United States.
Int Rev Neurobiol. 2019;145:127-176. doi: 10.1016/bs.irn.2019.05.002. Epub 2019 Jun 6.
Peripheral neuropathy is a common and debilitating complication of diabetes and prediabetes. Recent clinical studies have identified an association between the development of neuropathy and dyslipidemia in prediabetic and diabetic patients. Despite the prevalence of this complication, studies identifying molecular mechanisms that underlie neuropathy progression in prediabetes or diabetes are limited. However, dysfunctional mitochondrial pathways in hereditary neuropathy provide feasible molecular targets for assessing mitochondrial dysfunction in neuropathy associated with prediabetes or diabetes. Recent studies suggest that elevated levels of dietary saturated fatty acids (SFAs) associated with dyslipidemia impair mitochondrial dynamics in sensory neurons by inducing mitochondrial depolarization, compromising mitochondrial bioenergetics, and impairing axonal mitochondrial transport. This causes lower neuronal ATP and apoptosis. Conversely, monounsaturated fatty acids (MUFAs) restore nerve and sensory mitochondrial function. Understanding the mitochondrial pathways that contribute to neuropathy progression in prediabetes and diabetes may provide therapeutic targets for the treatment of this debilitating complication.
周围神经病变是糖尿病和糖尿病前期常见且使人虚弱的并发症。最近的临床研究表明，在糖尿病前期和糖尿病患者中，神经病与血脂异常之间存在关联。尽管这种并发症很普遍，但研究确定导致糖尿病前期或糖尿病神经病变进展的分子机制的研究有限。然而，遗传性神经病中功能失调的线粒体途径为评估与糖尿病前期或糖尿病相关神经病中的线粒体功能障碍提供了可行的分子靶标。最近的研究表明，血脂异常相关的膳食饱和脂肪酸 (SFA) 水平升高会通过诱导线粒体去极化、损害线粒体生物能学和损害轴突线粒体运输来损害感觉神经元中的线粒体动力学，从而导致神经元 ATP 水平降低和细胞凋亡。相反，单不饱和脂肪酸 (MUFA) 可恢复神经和感觉线粒体功能。了解导致糖尿病前期和糖尿病神经病变进展的线粒体途径可能为治疗这种使人虚弱的并发症提供治疗靶点。
