| First Author | Bidhendi EE | Year | 2016 |
| Journal | J Clin Invest | Volume | 126 |
| Issue | 6 | Pages | 2249-53 |
| PubMed ID | 27140399 | Mgi Jnum | J:237077 |
| Mgi Id | MGI:5810842 | Doi | 10.1172/JCI84360 |
| Citation | Bidhendi EE, et al. (2016) Two superoxide dismutase prion strains transmit amyotrophic lateral sclerosis-like disease. J Clin Invest 126(6):2249-53 |
| abstractText | 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. |
