title: Axonal degeneration in multiple sclerosis: defining therapeutic targets by identifying the causes of pathology.
abstract: Current therapeutics in multiple sclerosis (MS) target the putative inflammation and immune attack on CNS myelin. Despite their effectiveness in blunting the relapse rate in MS patients, such therapeutics do not prevent MS disease progression. Importantly, specific clinical dilemma arises through inability to predict MS progression and thereby therapeutically target axonal injury during MS, limiting permanent disability. The current review identifies immune and neurobiological principles that govern the sequelae of axonal degeneration during MS disease progression. Defining the specific disease arbiters, inflammatory and autoimmune, oligodendrocyte dystrophy and degenerative myelin, we discuss a basis for a molecular mechanism in axons that may be targeted therapeutically, in spatial and temporal manner to limit axonal degeneration and thereby halt progression of MS.
authors.affiliation: Department of Medicine, Central Clinical School, Monash University, Prahran VIC 3004, Australia.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Medicine, Central Clinical School, Monash University, Prahran VIC 3004, Australia.
authors.forename: Melissa
authors.initials: M
authors.lastname: Biemond
authors.affiliation: Department of Medicine, Central Clinical School, Monash University, Prahran VIC 3004, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Petratos
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
keywords: CD8 T cells; Nogo receptor 1; NogoA; Th17 T cells; axo-glial unit; axonal degeneration; experimental autoimmune encephalomyelitis; myelin debris; oligodendrocyte dystrophy; progressive multiple sclerosis