Mechanism and treatment progress of endoplasmic reticulum stress pathway in diabetic neuropathy

Diabetic neuropathy (DN) is one of the most common chronic complications of diabetes, severely impacting patients’ quality of life. Recent studies have demonstrated that endoplasmic reticulum stress (ERS) plays a key role in the development and progression of DN. This article systematically reviews the activation mechanisms of the ERS pathway, its pathological role in DN, and potential therapeutic strategies targeting this pathway. The ER, a crucial site for protein synthesis, folding, and modification in eukaryotic cells, is homeostatically imbalanced, triggering the unfolded protein response (UPR). In the diabetic state, chronic hyperglycemia, oxidative stress, inflammatory factors, and other factors lead to persistent activation of ERS. Through signaling pathways such as PERK, IRE1α, and ATF6, ERS ultimately causes neuronal and Schwann cell apoptosis, mitochondrial dysfunction, and neuroinflammation, promoting the progression of DN. A deeper understanding of the relationship between ERS and DN will not only help elucidate disease mechanisms but also provide a theoretical basis for the development of novel targeted therapies.Diabetic neuropathy (DN) is one of the most common chronic complications of diabetes, severely impacting patients’ quality of life. Recent studies have demonstrated that endoplasmic reticulum stress (ERS) plays a key role in the development and progression of DN. This article systematically reviews the activation mechanisms of the ERS pathway, its pathological role in DN, and potential therapeutic strategies targeting this pathway. The ER, a crucial site for protein synthesis, folding, and modification in eukaryotic cells, is homeostatically imbalanced, triggering the unfolded protein response (UPR). In the diabetic state, chronic hyperglycemia, oxidative stress, inflammatory factors, and other factors lead to persistent activation of ERS. Through signaling pathways such as PERK, IRE1α, and ATF6, ERS ultimately causes neuronal and Schwann cell apoptosis, mitochondrial dysfunction, and neuroinflammation, promoting the progression of DN. A deeper understanding of the relationship between ERS and DN will not only help elucidate disease mechanisms but also provide a theoretical basis for the development of novel targeted therapies.