Pharmacological Modulation of Oxidative Stress, Neuroinflammation, and Synaptic Dysfunction for Precision Neuroprotection in Neurodegenerative Disorders: A Narrative Review

Neurodegenerative diseases such as Alzheimer’s and Parkinson’s remain major global challenges, characterized by progressive neuronal loss and cognitive decline in the aging population. Among their core pathogenic mechanisms, oxidative stress, neuroinflammation, and synaptic dysfunction play pivotal and interconnected roles. Pharmacological modulation of these pathways offers potential avenues for neuroprotection and therapeutic intervention. Antioxidant defence mechanisms, particularly the *Nrf2*/*HO-1* signaling axis, are essential in maintaining redox homeostasis and cellular integrity. Likewise, regulation of neuroinflammatory cascades involving *NF-κB* and pro-inflammatory cytokines may prevent sustained neuronal injury. Restoration of synaptic function through neurotrophic factors such as *BDNF* and modulation of dopaminergic neurotransmission further contributes to neuronal resilience. This narrative review summarizes current advances in understanding these mechanisms and explores both natural compounds and synthetic small molecules demonstrating preclinical or early translational potential. Despite challenges related to dosing, target specificity, and long-term safety, emerging multi-targeted pharmacological strategies hold significant promise for precision neuroprotection and improved brain health in neurodegenerative disorders. This narrative review follows the SANRA framework to ensure methodological transparency.