Disorders of mitochondrial dynamics in peripheral neuropathy: Clues from hereditary neuropathy and diabetes.

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.