Familial amyotrophic lateral sclerosis associated with mutant Cu/Zn superoxide dismutase as a conformational disease
Koide, T.; Igarashi, S.; Kikugawa, K.; Nakano, R.; Inuzuka, T.; Tsuji, S.; Yamada, M.; Takahashi, H.
Rinsho Shinkeigaku 39(12): 1283-1284
1999
ISSN/ISBN: 0009-918X PMID: 10791098 Document Number: 498695
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.