We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Two superoxide dismutase prion strains transmit amyotrophic lateral sclerosis-like disease.
- Authors
Ekhtiari Bidhendi, Elaheh; Bergh, Johan; Zetterström, Per; Andersen, Peter M.; Marklund, Stefan L.; Brännström, Thomas; Bidhendi, Elaheh Ekhtiari
- Abstract
Amyotrophic lateral sclerosis (ALS) is an adult-onset degeneration of motor neurons that is commonly caused by mutations in the gene encoding superoxide dismutase 1 (SOD1). Both patients and Tg mice expressing mutant human SOD1 (hSOD1) develop aggregates of unknown importance. In Tg mice, 2 different strains of hSOD1 aggregates (denoted A and B) can arise; however, the role of these aggregates in disease pathogenesis has not been fully characterized. Here, minute amounts of strain A and B hSOD1 aggregate seeds that were prepared by centrifugation through a density cushion were inoculated into lumbar spinal cords of 100-day-old mice carrying a human SOD1 Tg. Mice seeded with A or B aggregates developed premature signs of ALS and became terminally ill after approximately 100 days, which is 200 days earlier than for mice that had not been inoculated or were given a control preparation. Concomitantly, exponentially growing strain A and B hSOD1 aggregations propagated rostrally throughout the spinal cord and brainstem. The phenotypes provoked by the A and B strains differed regarding progression rates, distribution, end-stage aggregate levels, and histopathology. Together, our data indicate that the aggregate strains are prions that transmit a templated, spreading aggregation of hSOD1, resulting in a fatal ALS-like disease.
- Subjects
SUPEROXIDE dismutase; AMYOTROPHIC lateral sclerosis; SPINAL cord; MOUSE diseases; LABORATORY mice
- Publication
Journal of Clinical Investigation, 2016, Vol 126, Issue 6, p2249
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI84360