title: Rifampicin reduces alpha-synuclein in a transgenic mouse model of multiple system atrophy.
abstract: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by oligodendrocytic cytoplasmic inclusions containing abnormally aggregated alpha-synuclein. This aggregation has been linked to the neurodegeneration observed in MSA. Current MSA treatments are aimed at controlling symptoms rather than tackling the underlying cause of neurodegeneration. This study investigates the ability of the antibiotic rifampicin to reduce alpha-synuclein aggregation and the associated neurodegeneration in a transgenic mouse model of MSA. We report a reduction in monomeric and oligomeric alpha-synuclein and a reduction in phosphorylated alpha-synuclein (S129) upon rifampicin treatment. This reduction in alpha-synuclein aggregation was accompanied by reduced neurodegeneration. On the basis of its anti-aggregenic properties, we conclude that rifampicin may have therapeutic potential for MSA.
authors.affiliation: Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, California, USA.
authors.forename: Kiren
authors.initials: K
authors.lastname: Ubhi
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.forename: Michael
authors.initials: M
authors.lastname: Mante
authors.forename: Christina
authors.initials: C
authors.lastname: Patrick
authors.forename: Anthony
authors.initials: A
authors.lastname: Adame
authors.forename: Monica
authors.initials: M
authors.lastname: Thukral
authors.forename: Clifford
authors.initials: C
authors.lastname: Shults
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000627:therapeutic use; D015153:Blotting, Western; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D019578:Multiple System Atrophy / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use*; D051843:Synucleins / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*; D051846:beta-Synuclein / Q000378:metabolism
chemical_list: D000904:Antibiotics, Antitubercular; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein; D012293:Rifampin