title: Recent advances in understanding the role of oxidative stress in diabetic neuropathy.
abstract: Diabetic neuropathy (DN) is one of the most common and severe manifestations of diabetes mellitus. The mechanisms underlying the structural, functional and metabolic changes in diabetic neuropathy have been under study for a long time. In this review the biochemistry and implications of the four pathways responsible for the development of DN, polyol pathway; increased AGEs (advanced glycation end-products) formation; activation of PKC (protein kinase C) and hexosamine pathway have been discussed. Experimental and clinical evidences suggest a close link between neurodegeneration and oxidative stress which serves as a unifying mechanism, thus linking the four pathways. Recent studies indicate that oxidative stress mediated DNA damage causes poly(ADP-ribose) polymerase (PARP) overactivation and reduced activity of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a factor common to all the four pathways. The exact mechanism of PARP mediated cell death in DN needs further investigation. Based on current studies neuroprotective and antioxidant therapy have been suggested as potential treatment and preventive solutions for DN.
authors.affiliation: Dr. BR Ambedkar Centre for Biomedical Research, University of Delhi, Delhi 110 007, India. Electronic address: manalshakeel@yahoo.com.
authors.forename: Manal
authors.initials: M
authors.lastname: Shakeel
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry; D011379:Prognosis
chemical_list: D000975:Antioxidants; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases
keywords: Diabetic neuropathy; Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) inhibition; Neurodegeneration; Oxidative stress; Poly(ADP-ribose) polymerase (PARP) overactivation