Autophagy in Schwann cells: A potential pharmacotherapeutic target in diabetic peripheral neuropathy

Figure 1 Autophagic imbalance leads to Schwann cell dysfunction. High glucose-induced oxidative stress triggers reactive oxygen species release, activates protein kinase B via phosphatidylinositol 3-kinase, inhibits tuberous sclerosis complex, and promotes mammalian target of rapamycin phosphorylation. Subsequently mRNA translation is enhanced and autophagosome formation is inhibited. Lysosomal damage induces transforming growth factor-β-activated protein kinase 1-galectin-9 binding, which activates adenosine monophosphate-activated protein kinase and unc-51-like kinase 1 to promote autophagy. Mitochondrial damage under high glucose leads to phosphatase and tensin homolog induced putative kinase 1 accumulation and parkin phosphorylation. AMPK: Adenosine monophosphate-activated protein kinase; mTOR: Mammalian target of rapamycin; PI3K: Phosphatidylinositol 3-kinase; ULK1: Unc-51-like kinase 1; ATG13: Autophagy related 13; FIP200: Focal adhesion kinase family kinase-interacting protein 200kD; ROS: Reactive oxygen species; SQSTM1: Sequestosome 1; LC3: Light chain 3; PINK1: Phosphatase and tensin homolog-induced putative kinase 1.