Redox environment is an intracellular factor to operate distinct pathways for aggregation of Cu,Zn-superoxide dismutase in amyotrophic lateral sclerosis
Dominant mutations in Cu,Zn-superoxide dismutase (SOD1) cause a familial form of amyotrophic lateral sclerosis (fALS). Misfolding and aggregation of mutant SOD1 proteins are a pathological hallmark of SOD1-related fALS cases; however, the molecular mechanism of SOD1 aggregation remains controversia...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-11-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00240/full |
| _version_ | 1817995616458899456 |
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| author | Yoshiaki eFurukawa |
| author_facet | Yoshiaki eFurukawa |
| author_sort | Yoshiaki eFurukawa |
| collection | DOAJ |
| description | Dominant mutations in Cu,Zn-superoxide dismutase (SOD1) cause a familial form of amyotrophic lateral sclerosis (fALS). Misfolding and aggregation of mutant SOD1 proteins are a pathological hallmark of SOD1-related fALS cases; however, the molecular mechanism of SOD1 aggregation remains controversial. Here, I have used E. coli as a model organism and shown multiple distinct pathways of SOD1 aggregation that are dependent upon its thiol-disulfide status. Overexpression of fALS-mutant SOD1s in the cytoplasm of E. coli BL21 and SHuffleTM, where redox environment is reducing and oxidizing, respectively, resulted in the formation of insoluble aggregates with notable differences; a disulfide bond of SOD1 was completely reduced in BL21 or abnormally formed between SOD1 molecules in SHuffleTM. Depending upon intracellular redox environment, therefore, mutant SOD1 is considered to misfold/aggregate through distinct pathways, which would be relevant in description of the pathological heterogeneity of SOD1-related fALS cases. |
| first_indexed | 2024-04-14T02:09:05Z |
| format | Article |
| id | doaj.art-50f23aac15584f1a812232c06badd663 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-14T02:09:05Z |
| publishDate | 2013-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-50f23aac15584f1a812232c06badd6632022-12-22T02:18:33ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022013-11-01710.3389/fncel.2013.0024063308Redox environment is an intracellular factor to operate distinct pathways for aggregation of Cu,Zn-superoxide dismutase in amyotrophic lateral sclerosisYoshiaki eFurukawa0Keio UniversityDominant mutations in Cu,Zn-superoxide dismutase (SOD1) cause a familial form of amyotrophic lateral sclerosis (fALS). Misfolding and aggregation of mutant SOD1 proteins are a pathological hallmark of SOD1-related fALS cases; however, the molecular mechanism of SOD1 aggregation remains controversial. Here, I have used E. coli as a model organism and shown multiple distinct pathways of SOD1 aggregation that are dependent upon its thiol-disulfide status. Overexpression of fALS-mutant SOD1s in the cytoplasm of E. coli BL21 and SHuffleTM, where redox environment is reducing and oxidizing, respectively, resulted in the formation of insoluble aggregates with notable differences; a disulfide bond of SOD1 was completely reduced in BL21 or abnormally formed between SOD1 molecules in SHuffleTM. Depending upon intracellular redox environment, therefore, mutant SOD1 is considered to misfold/aggregate through distinct pathways, which would be relevant in description of the pathological heterogeneity of SOD1-related fALS cases.http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00240/fullAmyloidAggregationALSSOD1disulfide bond |
| spellingShingle | Yoshiaki eFurukawa Redox environment is an intracellular factor to operate distinct pathways for aggregation of Cu,Zn-superoxide dismutase in amyotrophic lateral sclerosis Frontiers in Cellular Neuroscience Amyloid Aggregation ALS SOD1 disulfide bond |
| title | Redox environment is an intracellular factor to operate distinct pathways for aggregation of Cu,Zn-superoxide dismutase in amyotrophic lateral sclerosis |
| title_full | Redox environment is an intracellular factor to operate distinct pathways for aggregation of Cu,Zn-superoxide dismutase in amyotrophic lateral sclerosis |
| title_fullStr | Redox environment is an intracellular factor to operate distinct pathways for aggregation of Cu,Zn-superoxide dismutase in amyotrophic lateral sclerosis |
| title_full_unstemmed | Redox environment is an intracellular factor to operate distinct pathways for aggregation of Cu,Zn-superoxide dismutase in amyotrophic lateral sclerosis |
| title_short | Redox environment is an intracellular factor to operate distinct pathways for aggregation of Cu,Zn-superoxide dismutase in amyotrophic lateral sclerosis |
| title_sort | redox environment is an intracellular factor to operate distinct pathways for aggregation of cu zn superoxide dismutase in amyotrophic lateral sclerosis |
| topic | Amyloid Aggregation ALS SOD1 disulfide bond |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00240/full |
| work_keys_str_mv | AT yoshiakiefurukawa redoxenvironmentisanintracellularfactortooperatedistinctpathwaysforaggregationofcuznsuperoxidedismutaseinamyotrophiclateralsclerosis |