ER Stress in Diabetic Peripheral Neuropathy: A New Therapeutic Target.
Authors O'Brien PD, Hinder LM, Sakowski SA, Feldman EL
Submitted By Eva Feldman on 4/15/2014
Status Published
Journal Antioxidants & redox signaling
Year 2014
Date Published 2/27/2014
Volume : Pages 21 : 621 - 633
PubMed Reference 24382087
Abstract Abstract Significance: Diabetes and other diseases that comprise the metabolic
syndrome have reached epidemic proportions. Diabetic peripheral neuropathy (DPN)
is the most prevalent complication of diabetes, affecting ~50% of diabetic
patients. Characterized by chronic pain or loss of sensation, recurrent foot
ulcerations, and risk for amputation, DPN is associated with significant
morbidity and mortality. Mechanisms underlying DPN pathogenesis are complex and
not well understood, and no effective treatments are available. Thus, an
improved understanding of DPN pathogenesis is critical for the development of
successful therapeutic options. Recent Advances: Recent research implicates
endoplasmic reticulum (ER) stress as a novel mechanism in the onset and
progression of DPN. ER stress activates the unfolded protein response (UPR), a
well-orchestrated signaling cascade responsible for relieving stress and
restoring normal ER function. Critical Issues: During times of extreme or
chronic stress, such as that associated with diabetes, the UPR may be
insufficient to alleviate ER stress, resulting in apoptosis. Here, we discuss
the potential role of ER stress in DPN, as well as evidence demonstrating how ER
stress intersects with pathways involved in DPN development and progression. An
improved understanding of how ER stress contributes to peripheral nerve
dysfunction in diabetes will provide important insight into DPN pathogenesis.
Future Directions: Future studies aimed at gaining the necessary insight into ER
stress in DPN pathogenesis will ultimately facilitate the development of novel
therapies. Antioxid. Redox Signal. 00, 000-000.

Investigators with authorship
Eva FeldmanUniversity of Michigan