title: Beta 2-adrenoceptor involvement in inflammatory demyelination and axonal degeneration in multiple sclerosis.
abstract: Relapses of multiple sclerosis (MS) are considered to be the clinical expression of acute T-cell-mediated inflammatory demyelinating lesions disseminated in the CNS, whereas disease progression seems to result from widespread axonal degeneration. The pathophysiology of both disease components is incompletely understood. Astrocytes in MS lack beta(2)-adrenoceptors, which via cAMP-mediated processes inhibit the expression of major histocompatibility (MHC) class II molecules and stimulate glycogenolysis in normal conditions. In a pro-inflammatory CNS environment this beta(2)-adrenoceptor defect might allow astrocytes to transform into facultative antigen-presenting cells that can initiate the inflammatory cascade. The same receptor defect might impair astrocytic glycogenolysis, which normally generates lactate that is transported to axons as an energy source. Failure of axonal energy metabolism might result in axonal degeneration through mechanisms that involve intra-axonal accumulation of Ca(2+) ions and mitochondrial dysfunction. If this hypothesis is correct, therapies designed to elevate cAMP levels in astrocytes should reduce or prevent both relapses and progression of MS.
authors.affiliation: Department of Neurology, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Jacques
authors.initials: J
authors.lastname: De Keyser
authors.forename: Esther
authors.initials: E
authors.lastname: Zeinstra
authors.forename: Jop
authors.initials: J
authors.lastname: Mostert
authors.forename: Nadine
authors.initials: N
authors.lastname: Wilczak
mesh_terms: D001253:Astrocytes / Q000502:physiology; D001369:Axons / Q000473:pathology*; D003711:Demyelinating Diseases / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D018343:Receptors, Adrenergic, beta-2 / Q000172:deficiency* / Q000502:physiology
chemical_list: D018343:Receptors, Adrenergic, beta-2