Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700 032, India.
Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700 032, India.
Eur J Pharmacol. 2018 Aug 15;833:472-523. doi: 10.1016/j.ejphar.2018.06.034. Epub 2018 Jun 30.
Diabetic neuropathy is regarded as one of the most debilitating outcomes of diabetes mellitus and may cause pain, decreased motility, and even amputation. Diabetic neuropathy includes multiple forms, ranging from discomfort to death. Prognosis of diabetic neuropathy is an uphill task as it remains silent for several years after the onset of diabetes. Hyperglycemia, apart from inducing oxidative stress in neurons, also leads to activation of multiple biochemical pathways which constitute the major source of damage and are potential therapeutic targets in diabetic neuropathy. A vast array of molecular pathways, including polyol pathway, hexosamine pathway, PKCs signaling, oxidative stress, AGEs pathway, PARP pathway, MAPK pathway, NF-κB signaling, hedgehog pathways, TNF-α signaling, cyclooxygenase pathway, interleukins, lipoxygenase pathway, nerve growth factor, Wnt pathway, autophagy, and GSK3 signaling may be accounted for the pathogenesis and progression of diabetic neuropathy. Although symptomatic treatment is available for diabetic neuropathy, few treatment options are available to eliminate the root cause. The immense physical, psychological, and economic burden of diabetic neuropathy highlights the need for cost effective and targeted therapies. The main aim of this review is to highlight the putative role of various mechanisms and pathways involved in the development of diabetic neuropathy and to impart an in-depth insight on new therapeutic approaches aimed at delaying or reversing various modalities of diabetic neuropathy.
糖尿病性神经病被认为是糖尿病最具致残性的后果之一，可能导致疼痛、运动能力下降，甚至截肢。糖尿病性神经病包括多种形式，从轻症到重症不等。糖尿病性神经病的预后是一项艰巨的任务，因为它在糖尿病发病后数年仍处于无声状态。高血糖除了在神经元中诱导氧化应激外，还会激活多种生化途径，这些途径构成了主要的损伤源，也是糖尿病性神经病潜在的治疗靶点。大量的分子途径，包括多元醇途径、己糖胺途径、PKC 信号通路、氧化应激、AGEs 途径、PARP 途径、MAPK 途径、NF-κB 信号通路、刺猬途径、TNF-α信号通路、环氧合酶途径、白细胞介素、脂氧合酶途径、神经生长因子、Wnt 途径、自噬和 GSK3 信号通路，可能与糖尿病性神经病的发病机制和进展有关。尽管有针对糖尿病性神经病的对症治疗方法，但消除根本原因的治疗选择很少。糖尿病性神经病给患者带来了巨大的身体、心理和经济负担，这凸显了需要有经济有效的靶向治疗方法。本综述的主要目的是强调参与糖尿病性神经病发展的各种机制和途径的作用，并深入了解旨在延缓或逆转各种糖尿病性神经病模式的新治疗方法。
