Targeting Neurodegeneration With Naringenin: Mechanistic Perspectives and Therapeutic Implications.
Neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, retinal neurodegeneration, and spinal cord injury represent a growing global health burden with limited therapeutic options. Natural compounds, particularly flavonoids, have emerged as promising neuroprotective agents. Naringenin (NAR), a citrus-derived flavanone, exhibits potent antioxidant, anti-inflammatory, and neuroprotective properties. Recent studies revealed that NAR modulates multiple cellular pathways, including oxidative stress reduction, mitochondrial protection, autophagy induction, inhibition of microglial activation, and suppression of neuroinflammatory signaling such as NF-κB and NLRP3 inflammasome. Furthermore, NAR has demonstrated the ability to reduce amyloid-β plaque deposition, inhibit α-synuclein aggregation, preserve dopaminergic neurons, modulate immune responses in multiple sclerosis, and improve functional recovery after spinal cord injury. This review comprehensively summarizes the mechanistic insights and therapeutic potential of NAR across various neurodegenerative diseases, highlighting its promise as a multifunctional neuroprotective agent and the need for further translational research.