Yerra Veera Ganesh, Gundu Chayanika, Bachewal Pragna, Kumar Ashutosh
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Bala Nagar, TG, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Bala Nagar, TG, India.
Med Hypotheses. 2016 Jan;86:120-8. doi: 10.1016/j.mehy.2015.11.004. Epub 2015 Nov 5.
Autophagy is a dynamic process which plays an important role in cellular homeostasis through recycling of damaged proteins and organelles. Chronic hyperglycemia associated with diabetes is known to impair the cellular autophagic pathways to a varied extent in some of the diabetic complications. But the role of autophagy driven quality control of proteins and the cellular organelles has been understudied in diabetic complications including neuropathy (DN). The present article hypothesizes that enhancing autophagy in neuronal cells may help them to get rid of bioenergetic crisis, necrosis, apoptosis associated with DN. Some forms of autophagic turnover also help to maintain integral, healthy mitochondria, malfunctioning of which produces cellular reactive oxygen species and may prevent accumulation of damaged protein aggregates. Involvement of various energy derived metabolic, cellular death pathways and oxidative stress in the pathogenesis of DN and how autophagy may halts the progression of DN has been discussed with supporting literature.
自噬是一个动态过程,通过回收受损蛋白质和细胞器在细胞内稳态中发挥重要作用。已知与糖尿病相关的慢性高血糖在某些糖尿病并发症中会不同程度地损害细胞自噬途径。但是,在包括神经病变(DN)在内的糖尿病并发症中,自噬驱动的蛋白质和细胞器质量控制的作用尚未得到充分研究。本文假设增强神经元细胞中的自噬可能有助于它们摆脱与DN相关的生物能量危机、坏死和凋亡。某些形式的自噬周转也有助于维持完整、健康的线粒体,线粒体功能异常会产生细胞活性氧,并可能防止受损蛋白质聚集体的积累。本文结合支持性文献讨论了各种能量衍生的代谢、细胞死亡途径和氧化应激在DN发病机制中的作用,以及自噬如何可能阻止DN的进展。