Neuroprotective Potential of Curcumin in Neurodegenerative Diseases: Clinical Insights Into Cellular and Molecular Signaling Pathways

ABSTRACT Progressive neuronal loss and dysfunction characterize neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, and Huntington's diseases, spinal cord injury, and stroke, making them difficult to treat. Curcumin, a bioactive substance derived from the turmeric plant ( Curcuma longa ), is interesting due to its potential neuroprotective properties. This review thoroughly shows the cellular and molecular signaling mechanisms that curcumin utilizes to provide neuroprotective effects in NDs. Curcumin regulates several signaling pathways linked to neuroprotection, such as those that reduce oxidative stress, prevent Aβ formation, and decrease neuroinflammation. NF‐κB suppression reduces inflammatory responses, while Nrf2 activation boosts antioxidant response element expression. Furthermore, curcumin enhances autophagy and neurotrophic factor expression, facilitating the removal of harmful protein aggregates. The function of curcumin as a metal chelator is emphasized particularly to iron and other metal dysregulations linked to neurodegenerative processes. Curcumin's capacity to regulate metal ion homeostasis is essential since the pathophysiology of NDs is significantly influenced by metal‐induced oxidative stress and toxic buildup. It shows potential therapeutic effects by reducing oxidative damage and chelating excess metals. Clinical research indicates that curcumin can penetrate the blood‐brain barrier, making it an effective treatment option. The regulation of these pathways reduces neuronal damage and improves neurons' survival and functionality. In addition, curcumin's anti‐inflammatory properties and low toxicity make it a promising long‐term treatment option for NDs. Therefore, this review emphasizes the potential of curcumin as a targeted neuroprotective compound, presenting recent clinical insights and experimental data. Future studies should optimize curcumin formulations and delivery systems to enhance its bioavailability and therapeutic efficacy.