Rifampicin reduces alpha-synuclein in a transgenic mouse model of multiple system atrophy.
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.
Ubhi
Kiren
K
Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, California, USA.
Rockenstein
Edward
E
Mante
Michael
M
Patrick
Christina
C
Adame
Anthony
A
Thukral
Monica
M
Shults
Clifford
C
Masliah
Eliezer
E
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
D000904:Antibiotics, Antitubercular; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein; D012293:Rifampin