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Moreover, EAE is characterized by a CD4 T lymphocytic preponderance in contrast to CD8 T cells in MS lesions ( Recently, a hybrid model (cuprizone autoimmune encephalitis or CAE) combining the myelin-toxic effects of cuprizone (Zirngibl et al., 2022) together with an immune stimulation identical to EAE but without extrinsic myelin peptides, provided proof-of-principle for the notion that a primary biochemical dysmyelination can result in a very typical inflammatory demyelinating white matter lesion in an immune-stimulated host ( BOX 1 The immunobiology of MS The immune-mediated biology of MS identifies a prominent role of peripherally-derived T and B cells in acute active demyelinating lesions, with microglia, macrophages and astrocytes mainly responsible for chronic inflammation (Rodrguez Mura et al., 2022

Tissue-level deficiency of cobalamin is associated with an increase in the urinary and serum concentrations of an organic acid called methylmalonic acid, which is an alternative product of a cobalamin dependent pathway within the mitochondria

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NAD+ biosynthesis, aging, and disease

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