Utility of Drosophila for studying hypoxia-inducible factor (HIF) in neurodegenerative diseases: Advantages versus limitations.

Hypoxia-inducible factor 1α (HIF-1α) plays a critical role in cellular responses to oxygen deprivation and is increasingly recognized as a key regulator in neurodegenerative diseases. Drosophila melanogaster serves as a powerful genetic model for investigating HIF-1α signaling, particularly through its homolog Sima. This review examines the advantages and limitations of using Drosophila to study HIF-1α in the context of neurodegeneration, with a focus on oxidative stress, autophagy, and mitochondrial dysfunction. We discuss the role of HIF-1α/Sima in modulating neuroprotective pathways, including its interactions with DJ-1 (also known as PARK7 Parkinson disease protein 7), SNCA (Alpha-synuclein), and the mTOR-autophagy axis. Moreover, we highlight the potential of Drosophila in elucidating hypoxia-mediated epigenetic modifications, non-coding RNA regulation, and metabolic adaptations relevant to neurodegenerative diseases. Understanding these mechanisms may provide insights into novel therapeutic approaches for the major neurodegenerative conditions in humans, such as Parkinson's disease and Alzheimer's disease.