Figure 1. Summary of recent findings in [3,5]. While it is unclear what are the initial inducer(s) of inflammation, injury or cell death in MS and other neurological diseases, release of alarmins such as ATP or IL-1β in the CNS promotes an inflammatory environment that leads to OxPC deposition. Excess OxPCs are neurotoxic and drive demyelination and neurodegeneration. Microglia are the predominant immune cells of the CNS responding to OxPCs; they are normally neuroprotective and help neutralize OxPCs by phagocytic clearance. In the aging CNS, microglia have significantly altered transcriptome and functions, including an upregulation of the gene Spp1, which encodes for osteopontin. Aging microglia and the overexpression of osteopontin in the aging CNS environment leads to a defective response against OxPCs, resulting in exacerbated neurodegeneration. Figure created at Biorender.com.