Unknown

Dataset Information

0

Mutant superoxide dismutase aggregates from human spinal cord transmit amyotrophic lateral sclerosis.


ABSTRACT: Motor neurons containing aggregates of superoxide dismutase 1 (SOD1) are hallmarks of amyotrophic lateral sclerosis (ALS) caused by mutations in the gene encoding SOD1. We have previously reported that two strains of mutant human (h) SOD1 aggregates (denoted A and B) can arise in hSOD1-transgenic models for ALS and that inoculation of such aggregates into the lumbar spinal cord of mice results in rostrally spreading, templated hSOD1 aggregation and premature fatal ALS-like disease. Here, we explored whether mutant hSOD1 aggregates with prion-like properties also exist in human ALS. Aggregate seeds were prepared from spinal cords from an ALS patient carrying the hSOD1G127Gfs*7 truncation mutation and from mice transgenic for the same mutation. To separate from mono-, di- or any oligomeric hSOD1 species, the seed preparation protocol included ultracentrifugation through a density cushion. The core structure of hSOD1G127Gfs*7 aggregates present in mice was strain A-like. Inoculation of the patient- or mouse-derived seeds into lumbar spinal cord of adult hSOD1-expressing mice induced strain A aggregation propagating along the neuraxis and premature fatal ALS-like disease (p?

SUBMITTER: Ekhtiari Bidhendi E 

PROVIDER: S-EPMC6280858 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Mutant superoxide dismutase aggregates from human spinal cord transmit amyotrophic lateral sclerosis.

Ekhtiari Bidhendi Elaheh E   Bergh Johan J   Zetterström Per P   Forsberg Karin K   Pakkenberg Bente B   Andersen Peter M PM   Marklund Stefan L SL   Brännström Thomas T  

Acta neuropathologica 20181003 6


Motor neurons containing aggregates of superoxide dismutase 1 (SOD1) are hallmarks of amyotrophic lateral sclerosis (ALS) caused by mutations in the gene encoding SOD1. We have previously reported that two strains of mutant human (h) SOD1 aggregates (denoted A and B) can arise in hSOD1-transgenic models for ALS and that inoculation of such aggregates into the lumbar spinal cord of mice results in rostrally spreading, templated hSOD1 aggregation and premature fatal ALS-like disease. Here, we expl  ...[more]

Similar Datasets

| S-EPMC4887173 | biostudies-literature
| S-EPMC3085063 | biostudies-literature
| S-EPMC2869360 | biostudies-literature
| S-EPMC3121531 | biostudies-literature
| S-EPMC5216565 | biostudies-literature
| S-EPMC3170534 | biostudies-literature
| S-EPMC1790867 | biostudies-literature
| S-EPMC2903422 | biostudies-literature
| S-EPMC2850267 | biostudies-literature
| S-EPMC4052194 | biostudies-literature