title: Novel therapeutic targets for axonal degeneration in multiple sclerosis.
abstract: Multiple sclerosis (MS) is a devastating neurological condition that mainly affects young adults and is associated with long-standing morbidity. The pathophysiology of MS is believed to involve immune-mediated multifocal lesions in the CNS that are characterized by inflammation, demyelination, and axonal injury. Most research efforts to date have concentrated on the mechanisms of immune-mediated demyelination, whereas mechanisms of axonal injury, the major determinant of neurological deficits in MS patients, have been elusive beyond observational analyses. This review discusses current understanding of the pathology and novel clinical investigations of axonal injury in MS and the commonly used MS animal model, experimental autoimmune encephalomyelitis. The review focuses on the etiology and the induction of axonal degeneration through molecular signaling cascades downstream of myelin-associated inhibitory factors. Defining and eventually elucidating the signaling pathways elicited during the onset and progression of MS may provide novel therapeutic strategies to limit axonal degeneration in the acute phase of the disease. Furthermore, blocking or potentiating specific signaling pathways, particularly those that mediate axon retraction and promote disassembly of the tubulin network, may promote regrowth of damaged axons in CNS regions affected by many acute and chronic disease processes.
authors.affiliation: Monash Immunology and Stem Cell Laboratories, Monash University, Clayton Victoria, Australia. steven.petratos@med.monash.edu.au
authors.forename: Steven
authors.initials: S
authors.lastname: Petratos
authors.forename: Michael F
authors.initials: MF
authors.lastname: Azari
authors.forename: Ezgi
authors.initials: E
authors.lastname: Ozturk
authors.forename: Roula
authors.initials: R
authors.lastname: Papadopoulos
authors.forename: Claude C A
authors.initials: CC
authors.lastname: Bernard
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009103:Multiple Sclerosis / Q000150:complications / Q000378:metabolism / Q000628:therapy; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D009185:Myelin Proteins