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Hyperglycemia is a major and common feature of type 1 and type 2 diabetes, with high concentrations of glucose directly and negatively affecting brain function via AGEs and reactive oxygen species (ROS) and promoting abnormal DNA modification 34

Nitric oxide also plays a role in iron trafficking because it mimics the consequences of iron starvation and triggers iron uptake by cells

Secondly, asparaginase depletion using L-asparaginase has been a very effective approach in treating hematologic malignancies with detailed toxicity profile and well-studied resistance mechanism

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doi: 10.3389/fphar.2026.1674533 Received 03 August 2025 Revised 04 February 2026 Accepted 06 February 2026 Published 11 March 2026 Volume 17 - 2026 Edited by Micha Tomczyk, Medical University of Bialystok, Poland Reviewed by Sidharth Prasad Mishra, University of South Florida, United States Qiao Zhang, Shaanxi University of Chinese Medicine, China Updates Copyright 2026 Peng, Jiang, Tan and Jiang

71 Therapeutic modulation of the autophagy-mitophagy axis in metabolic diseases Pharmacological interventions Several pharmacological agents already in clinical use exert metabolic benefits, at least in part, through activation of autophagy and mitophagy