Niraj Kumar Singh, Ghaleb Oriquat, Ishika Jain, Mahima Chaudhary, Yasser Mohsen Khlyl, Navin Kumar Tailor
Neuroinflammation is the body's immune reaction that occurs inside the central nervous system to keep brain cells balanced and healthy. Uncontrolled and chronic neuroinflammation can start damaging neuronal cells and lead to neurodegenerative diseases. Glial cells, especially microglia and astrocytes, play an important role in this process. Microglia act as immune guards of the brain, shifting between protective and harmful states depending on certain signals such as NADPH oxidase 2, histone deacetylases, and transforming growth factor. Astrocytes support neurons and maintain the blood-brain barrier. During injury or stress, they become overactive and release numerous chemicals that make inflammation worse. Further, neuroinflammation is controlled by several signalling pathways, including NF-κB, PI3K/Akt, and MAPK. When these systems lose their balance, they cause ongoing inflammation and oxidative stress, which eventually harm brain cells. During the progression of neurodegenerative disorders, especially Alzheimer's Disease (AD) and Parkinson's Disease (PD), overactive microglia and astrocytes release large amounts of cytokines, reactive oxygen species, and inflammasome components that speed up neuron loss. The constant interaction between NF-κB, NLRP3, and oxidative stress worsens this damage, linking faulty molecular signals with the progression of these disorders. Ferulic acid, a natural antioxidant found in grains, fruits, and vegetables, has shown remarkable protective effects on the brain. It is biologically synthesized from aromatic amino acids L-phenylalanine and L-tyrosine through the shikimate pathway. By clearing free radicals and stopping lipid damage, ferulic acid protects neurons from degeneration. Experimental studies have shown that ferulic acid offers significant antioxidant and anti-neuroinflammatory effects and prevents the accumulation of harmful proteins, such as Aβ and α-synuclein, in the brain. Furthermore, ferulic acid has a strong capacity to modulate several cellular and molecular signaling pathways, including Nrf2/HO-1, NF-κB, and MAPK, which are closely linked to the development and progression of neurodegenerative disorders such as AD and PD. Interestingly, ferulic acid inhibits the generation of pro-inflammatory mediators, ameliorates mitochondrial dysfunction, prevents apoptosis, and consequently protects cholinergic and dopaminergic neurons in the brain, thereby exhibiting remarkable neuroprotective effects. Thus, the current review addressed that ferulic acid is considered a promising natural compound that could be an alternative natural phytoconstituent for the prevention and management of neuroinflammationassociated neurodegenerative disorders like AD and PD.