New perspective on neurodegenerative diseases: Focusing on the interaction between autophagy and oxidative stress and targeted strategies.

Autophagy is a highly conserved lysosome-dependent degradation process that plays a crucial role in maintaining neuronal homeostasis and adaptation during stress by eliminating misfolded proteins, damaged organelles, and pathogens. Oxidative stress, triggered by an imbalance between reactive oxygen speciesreactive oxygen species:ROS (ROS) production and antioxidant defenses, contributes to disease pathogenesis through mechanisms such as lipid peroxidation, protein carbonylation, and mitochondrial DNA damage. Recent studies reveal that autophagy and oxidative stress interact via a dynamic bidirectional regulatory network to modulate neurodegenerative pathology: ROS activate autophagy by regulating signaling pathways and modifying autophagy-associated proteins, while moderate autophagic activity selectively clears ROS-generating components and activates antioxidant pathways. Dysregulation of autophagy or excessive ROS accumulation can disrupt this equilibrium, leading to cell death and disorders such as neurodegenerative diseases, cancer, and aging-related pathologies. They reciprocally serve as "pressure signals" and "clearance targets", synergistically maintaining cellular homeostasis. This review synthesizes insights from current studies to systematically analyze the complex cross-talk between autophagy and oxidative stress in neurodegeneration and evaluates emerging therapeutic strategies targeting this interplay, including autophagy modulators, antioxidants, phytochemicals, and nanomaterials. These advancements offer novel perspectives for developing neuroprotective therapies through therapeutic modulation of the autophagy-oxidative stress axis. Finally, we summarize key challenges in the field and propose potential directions for future research.

• Publication year

  2026

• Venue

  Neurobiology of Disease

• Publication date

  2026-01-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.nbd.2026.107283PMID 41571053
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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