| Title : Trypanosome alternative oxidase, a potential therapeutic target for sleeping sickness, is conserved among Trypanosoma brucei subspecies - Nakamura_2010_Parasitol.Int_59_560 |
| Author(s) : Nakamura K , Fujioka S , Fukumoto S , Inoue N , Sakamoto K , Hirata H , Kido Y , Yabu Y , Suzuki T , Watanabe Y , Saimoto H , Akiyama H , Kita K |
| Ref : Parasitol Int , 59 :560 , 2010 |
|
Abstract :
Trypanosoma brucei rhodesiense and T. b. gambiense are known causes of human African trypanosomiasis (HAT), or "sleeping sickness," which is deadly if untreated. We previously reported that a specific inhibitor of trypanosome alternative oxidase (TAO), ascofuranone, quickly kills African trypanosomes in vitro and cures mice infected with another subspecies, non-human infective T. b. brucei, in in vivo trials. As an essential factor for trypanosome survival, TAO is a promising drug target due to the absence of alternative oxidases in the mammalian host. This study found TAO expression in HAT-causing trypanosomes; its amino acid sequence was identical to that in non-human infective T. b. brucei. The biochemical understanding of the TAO including its 3 dimensional structure and inhibitory compounds against TAO could therefore be applied to all three T. brucei subspecies in search of a cure for HAT. Our in vitro study using T. b. rhodesiense confirmed the effectiveness of ascofuranone (IC(50) value: 1 nM) to eliminate trypanosomes in human infective strain cultures. |
| PubMedSearch : Nakamura_2010_Parasitol.Int_59_560 |
| PubMedID: 20688188 |
| Gene_locus related to this paper: acreg-ascc |
| Gene_locus | acreg-ascc |
Nakamura K, Fujioka S, Fukumoto S, Inoue N, Sakamoto K, Hirata H, Kido Y, Yabu Y, Suzuki T, Watanabe Y, Saimoto H, Akiyama H, Kita K (2010)
Trypanosome alternative oxidase, a potential therapeutic target for sleeping sickness, is conserved among Trypanosoma brucei subspecies
Parasitol Int
59 :560
Nakamura K, Fujioka S, Fukumoto S, Inoue N, Sakamoto K, Hirata H, Kido Y, Yabu Y, Suzuki T, Watanabe Y, Saimoto H, Akiyama H, Kita K (2010)
Parasitol Int
59 :560