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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sun, Ying Zou, Yiyang Drenner, Kevin Tokunaga, Seiya Wang, Yin Kaspar, Brian K. Cleveland, Don W. Ling, Shuo-chien Ferraiuolo, Laura Lagier-tourenne, Clotilde Sun, Shuying Kopelevich, Alex Mcalonis-downes, Melissa Ditsworth, Dara |
| Description | Author Affiliation: Sun S ( Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093); Sun Y ( Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093); Ling SC ( Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093); Ferraiuolo L ( The Research Institute at Nationwide Children's Hospital, Department of Neuroscience, The Ohio State University, Columbus, OH 43205); McAlonis-Downes M ( Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093); Zou Y ( Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093); Drenner K ( Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093); Wang Y ( Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093); Ditsworth D ( Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093); Tokunaga S ( Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093); Kopelevich A ( Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093); Kaspar BK ( The Research Institute at Nationwide Children's Hospital, Department of Neuroscience, The Ohio State University, Columbus, OH 43205); Lagier-Tourenne C ( Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093); Cleveland DW ( Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093); |
| Abstract | Ubiquitous expression of amyotrophic lateral sclerosis (ALS)-causing mutations in superoxide dismutase 1 (SOD1) provokes noncell autonomous paralytic disease. By combining ribosome affinity purification and high-throughput sequencing, a cascade of mutant SOD1-dependent, cell type-specific changes are now identified. Initial mutant-dependent damage is restricted to motor neurons and includes synapse and metabolic abnormalities, endoplasmic reticulum (ER) stress, and selective activation of the PRKR-like ER kinase (PERK) arm of the unfolded protein response. PERK activation correlates with what we identify as a naturally low level of ER chaperones in motor neurons. Early changes in astrocytes occur in genes that are involved in inflammation and metabolism and are targets of the peroxisome proliferator-activated receptor and liver X receptor transcription factors. Dysregulation of myelination and lipid signaling pathways and activation of ETS transcription factors occur in oligodendrocytes only after disease initiation. Thus, pathogenesis involves a temporal cascade of cell type-selective damage initiating in motor neurons, with subsequent damage within glia driving disease propagation. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 50 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Amyotrophic Lateral Sclerosis Genetics Gene Expression Profiling Motor Neurons Metabolism Mutation Neuroglia Protein Biosynthesis Superoxide Dismutase Pathology Animals Astrocytes Mice Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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