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Historically known for its role in blood coagulationand bone formation,vitamin K (VK) has begun to emerge as an important nutrient for brainfunction. While VK involvement in the brain has not been fully explored,it is well-known that oxidative stress plays a critical role in neurodegenerativediseases. It was recently reported that VK protects neurons and oligodendrocytesfrom oxidative injury and rescues Drosophilafrom mitochondrial defects associated with Parkinson’s disease.In this study, we take a chemical approach to define the optimal andminimum pharmacophore responsible for the neuroprotective effectsof VK. In doing so, we have developed a series of potent VK analogueswith favorable drug characteristics that provide full protection atnanomolar concentrations in a well-defined model of neuronal oxidativestress. Additionally, we have characterized key cellular responsesand biomarkers consistent with the compounds’ ability to rescuecells from oxidative stress induced cell death. [ABSTRACT FROM AUTHOR]

Background: Central nervous system (CNS) infiltration by CD8 T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8 T cells in the CNS during acute HIV infection (AHI) is unknown., Methods: We analyzed the phenotype, gene expression, T cell receptor (TCR) repertoire, and HIV specificity of CD8 T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of AHI (n = 26), chronic (n = 23), and uninfected (n = 8)., Results: CSF CD8 T cells were elevated in AHI compared with uninfected controls. The frequency of activated CSF CD8 T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8 T cells during chronic HIV infection were associated with markers of neurological injury and microglial activation. CSF CD8 T cells in AHI exhibited increased functional gene expression profiles associated with CD8 T cells effector function, proliferation, and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8 T cells directed to unique HIV epitopes compared with the periphery., Conclusions: These results suggest that CSF CD8 T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in chronic HIV infection if combination antiretroviral therapy is initiated early.