Neuroinflammation plays a critical role in the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review explores the underlying mechanisms of neuroinflammation, with a focus on the roles of microglia, astrocytes, peripheral immune cell infiltration, and cytokine release. The complex interplay between oxidative stress and chronic inflammation accelerates neurodegeneration, contributing to disease progression. Microglial activation, initially protective, becomes harmful when sustained over time, driving chronic inflammation. Similarly, astrocytes once considered passive are now recognized for their active involvement in both inflammatory and neuroprotective responses, depending on their activation state. Prolonged activation of microglia and astrocytes compromises blood–brain barrier integrity, facilitating immune cell infiltration and amplifying inflammatory cascades, thereby worsening neuronal damage. We also detail the molecular mediators of the vicious cycle linking oxidative stress and chronic inflammation, including redox-sensitive transcription factors and mitochondrial dysfunction. Furthermore, the reviewed mechanisms highlight a pathogenic feedback loop, wherein oxidative stress and neuroinflammation fuel each other through NF-κ B and Nrf2 pathways, suggesting that dual-target therapeutic strategies may be most effective. This review synthesizes evidence to propose that the failure to resolve neuroinflammation, driven by a self-reinforcing loop between oxidative stress and glial dysfunction, represents a critical, targetable node common to PD, AD, and MS.
Mohannad A. Almikhlafi (Thu,) studied this question.