Effects of interferon-beta-1a on neuronal survival under autoimmune inflammatory conditions.
Interferon-beta-1a (IFN-beta-1a) is an approved treatment for multiple sclerosis (MS). It improves the disease course by reducing the relapse rate as well as the persistent neurological deficits. Recent MRI and post-mortem studies revealed that neuronal and axonal damage are most relevant for chronic disability in MS patients. We have characterized previously time course and mechanisms of neuronal apoptosis in a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced optic neuritis. In this animal model, application of IFN-beta-1a three times per week slightly decreases the loss of retinal ganglion cells (RGCs), the neurons that form the axons within the optic nerve. In contrast to neurotrophic factors, this cytokine does not directly protect cultured RGCs from apoptosis. We conclude that IFN-beta-1a is a suitable candidate to be combined with a directly neuroprotective agent in order to further decrease axonal and neuronal degeneration in MS patients.
Sättler
Muriel B
MB
Neurologische Universitätsklinik, Robert-Koch-Str. 40, 37075 Göttingen, Germany. msaettl@gwdg.de
Demmer
Iris
I
Williams
Sarah K
SK
Maier
Katharina
K
Merkler
Doron
D
Gadjanski
Ivana
I
Stadelmann
Christine
C
Bähr
Mathias
M
Diem
Ricarda
R
D000818:Animals; D000906:Antibodies / Q000097:blood; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011914:Rats, Inbred BN; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000906:Antibodies; C571326:MOG protein, human; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016899:Interferon-beta; D019950:Mitogen-Activated Protein Kinase 1; D000068556:Interferon beta-1a