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Current Drug Targets

Eiditor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Pro-Inflammatory Mechanisms in Diabetic Neuropathy: Focus on the Nuclear Factor Kappa B Pathway

Author(s): Norman E. Cameron and Mary A. Cotter

Volume 9 , Issue 1 , 2008

Page: [60 - 67] Pages: 8

DOI: 10.2174/138945008783431718

Price: $58

Abstract

Neuropathy is a common complication of diabetes mellitus, which reduces the quality of life and may be lifethreatening. 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 κ B (NFκB) 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 NFκB activation itself, or the production of cytokines that stimulate NFκB, such as tumor necrosis factor (TNF) α. To date there have been few tests of drugs that are specific inhibitors of the NFκB / TNFα axis. However preliminary results in animal models are encouraging and go some way in establishing the NFκB cascade as an important therapeutic target for diabetic vascular complications in general, and neuropathy in particular.

Keywords: p38 MAPK inhibitors, COX 2, nuclear peroxisome proliferator activated receptor, nerve conduction velocity, I kappa B kinase 2


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