Elevation of the Hsp70 chaperone does not effect toxicity in mouse models of familial amyotrophic lateral sclerosis
| Autor: | Darren Young, Don W. Cleveland, Leslie A. Shinobu, Jian Liu, Christopher M. Ward |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Genetically modified mouse
Blotting Western Mutant SOD1 Mice Transgenic Protein aggregation Biology Biochemistry Superoxide dismutase Mice Cellular and Molecular Neuroscience Superoxide Dismutase-1 Heat shock protein medicine Animals HSP70 Heat-Shock Proteins HSP90 Heat-Shock Proteins Age of Onset Amyotrophic lateral sclerosis Heat-Shock Proteins Motor Neurons Behavior Animal Superoxide Dismutase Amyotrophic Lateral Sclerosis Body Weight Age Factors Brain nutritional and metabolic diseases HSP40 Heat-Shock Proteins medicine.disease Immunohistochemistry Hsp70 Cell biology Mice Inbred C57BL Disease Models Animal Gene Expression Regulation Spinal Cord nervous system Immunology biology.protein Psychomotor Performance |
| Zdroj: | Journal of Neurochemistry. 93:875-882 |
| ISSN: | 1471-4159 0022-3042 |
| Popis: | Mutations in copper/zinc superoxide dismutase (SOD1) account for 10-20% of a familial form of amyotrophic lateral sclerosis (ALS). A common feature of SOD1 mutants is abnormal aggregation of the aberrant SOD1 in neurons and glia. We now report that in ALS transgenic mouse models the constitutively expressed heat shock protein 70 (Hsp70) is mislocalized into aggregates together with mutant SOD1 and ubiquitin. Forcing increased synthesis of Hsp70 ameliorates both aggregate formation and toxicity in primary motor neurons in culture. However, chronic increase in an inducible form of Hsp70 to about 10-fold its normal level is shown here not to affect disease course or pathology developed in mice from accumulation of any of three familial ALS causing SOD1 mutants with different underlying biochemical characteristics. Therefore, increasing Hsp70 to a level that is protective in mouse models of acute ischemic insult and selected neurodegenerative disorders is not sufficient to ameliorate mutant SOD1-mediated toxicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text