Neuroinflammation and Oxidative Stress: Their Pathophysiological Roles in Amyotrophic Lateral Sclerosis and Alzheimer’s Disease

Neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s disease (AD) are driven by complex, multifactorial mechanisms in which oxidative stress (OS) and neuroinflammation (NI) play central, mutually reinforcing roles. Their interaction is mediated through key signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nuclear factor erythroid 2–related factor 2–Kelch-like ECH-associated protein 1 (Nrf2-Keap1), and the mitogen-activated protein kinase (MAPK) pathway, as well as mitochondrial dysfunction, microglial activation, and dysregulated redox homeostasis. Increasing attention has been directed toward understanding how Food and Drug Administration (FDA)-approved neuroprotective agents influence these interconnected processes. Drugs such as riluzole, edaravone, memantine, and acetylcholinesterase inhibitors exhibit diverse effects on glutamate excitotoxicity, free radical production, inflammatory cytokine release, and microglial reactivity, yet their modest clinical efficacy highlights the limitations of single-target approaches. This review synthesizes current evidence on the mechanistic relationship between OS and NI in ALS and AD and evaluates how existing therapeutics modulate these pathways, emphasizing the need for multitarget strategies to achieve meaningful disease-modifying outcomes.