Effects of tetrahydrobiopterin on ataxia in Machado-Joseph disease may be based upon the theory of 'cerebellar long-term depression'.
We previously verified the effectiveness of tetrahydrobiopterin (BH4) on the ataxia in Machado-Joseph disease (MJD; SCA3 [spinocerebellar ataxia type 3]) as one of the most common types of dominantly inherited spinocerebellar ataxias. We hypothesized as to the pharmacological mechanism of BH4 that on the basis of 'cerebellar long-term depression' theory, BH4 may exert its actions at the levels of soluble guanylate cyclase in the Purkinje cells and of nitric oxide synthase in the granule cells. If cerebellar long-term depression is the case as the theoretical basis of BH4, it will open a new page of therapeutic strategy for spinocerebellar ataxias.
Sakai
T
T
Department of Neurology, National Chikugo Hospital, Chikugo City, Fukuoka Prefecture, Japan. sakait@tikugo.hosp.go.ip
D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000503:physiopathology; D018592:Cross-Over Studies; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology; D004311:Double-Blind Method; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D017827:Machado-Joseph Disease / Q000188:drug therapy* / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010919:Placebos; D011689:Purkinje Cells / Q000187:drug effects / Q000201:enzymology
D010919:Placebos; D001708:Biopterins; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; C003402:sapropterin