Pro-inflammatory mechanisms in diabetic neuropathy: focus on the Nuclear Factor Kappa B Pathway

Neuropathy is a common complication of diabetes mellitus, which reduces the quality of life and may be life-threatening. The etiology is complex and multifactorial: hyperglycemia and dyslipidemia give rise to oxidative stress and formation of advanced glycation and lipoxidation end products. These stimulate inflammatory processes, nuclear factor B (NF kappa B) activation being of central importance. Many of the drugs that have been developed for treatment of diabetic complication at least in part work through suppressing either NF kappa B activation itself, or the production of cytokines that stimulate NF kappa B, such as tumor necrosis factor (TNF) alpha. To date there have been few tests of drugs that are specific inhibitors of the NF kappa B/TNF alpha axis. However preliminary results in animal models are encouraging and go some way in establishing the NF kappa B cascade as an important therapeutic target for diabetic vascular complications in general, and neuropathy in particular.