Modulation of Neuroinflammation and Oxidative Stress as a Therapeutic Strategy in Parkinson’s Disease: Molecular Insights and Experimental Approaches

Abstract

Parkinson's disease (PD) is a progressive, multifactorial neurodegenerative illness that causes both motor and non-motor symptoms in addition to the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Growing data points to oxidative stress and neuroinflammation as important and related factors in the pathophysiology of Parkinson's disease. The activation of inflammasomes like NLRP3, microglial activation, and increased production of pro-inflammatory cytokines (like IL-1β and TNF-α) all contribute to a proinflammatory environment that worsens neuronal damage. A self-replicating cycle of neurotoxicity is produced when oxidative damage and lipid peroxidation are exacerbated by the buildup of reactive oxygen and nitrogen species (ROS/RNS), compromised mitochondrial function, and compromised antioxidant defense systems (e.g., SOD, GSH, catalase).The pathological interaction between neuroinflammation and oxidative stress is highlighted in this review, along with the ways in which they work together to promote α-synuclein aggregation, mitochondrial dysfunction, and disruption of the blood-brain barrier. The importance of these pathways in dopaminergic neurodegeneration has been clarified by preclinical models such as 6-OHDA, MPTP, rotenone, and LPS-induced neuroinflammation. We also assess new therapeutic approaches that target these mechanisms, such as NSAIDs, NLRP3 inhibitors, antioxidant treatments, natural polyphenolic compounds, and agents that target the mitochondria. Combining personalized medicine techniques with combination therapy may offer a more successful paradigm for altering the course of disease. A promising path toward neuroprotection and better results in Parkinson's disease is to target oxidative stress and neuroinflammation.