Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes. DPN is the commonest cause of neuropathy worldwide accounting for about 75% of the diabetic neuropathies. The most critical complications of DPN include foot ulcers, Charcot foot abnormalities, injuries, and eventually, lower-extremity amputation, especially when concomitant peripheral vascular disease causes foot ischemia.
S100P, a 95 amino acid protein, functions as intracellular regulator of diverse cellular processes including protein phosphorylation, cytoskeletal function, and protection from oxidative cell damage. S100P can act in an autocrine manner through binding to receptor for advanced glycation end products (RAGE). RAGE is the main receptor through which AGE signalling, one of the main pathophysiological mechanisms of diabetes and DPN, is mediated. This activation of RAGE by the S100P may be a source of underlying neuropathy in diabetes through their contribution to oxidative stress, activation of caspase-3 and changes induced in the DNA molecules. So, distorted expression of the S100P may be implicated in the pathogenesis of DPN through activation of the advanced glycation end products-RAGE alliance.