[Familial amyotrophic lateral sclerosis associated with mutant Cu/Zn superoxide dismutase as a conformational disease].
To investigate the molecular mechanism of mutant Cu/Zn superoxide dismutase (SOD) associated with familial amyotrophic lateral sclerosis (FALS), mutant (A1a4Thr, Gly85Arg, Gly93Ala, and two base-pair deletion in the 126th codon), as well as wild-type (wt), Cu/Zn SODs were expressed in COS7 cells. The formation of granular cytoplasmic aggregates accompanied by collapse of the cytoplasm was observed in cells expressing mutant Cu/Zn SODs, but not in cells expressing mutant Cu/Zn SODs. The aggregates contained ribosome-like particles and endoplasmic reticulum. These results suggest the possibility that mutant Cu/Zn SODs promote the formation of aggregates which are toxic to cells.
Koide
T
T
Department of Neurology, Niigata University, Japan.
Igarashi
S
S
Kikugawa
K
K
Nakano
R
R
Inuzuka
T
T
Tsuji
S
S
Yamada
M
M
Takahashi
H
H
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D013482:Superoxide Dismutase / Q000235:genetics*
D013482:Superoxide Dismutase