Over-expression of Hsp27 does not influence disease in the mutant SOD1(G93A) mouse model of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a chronic, adult-onset neurodegenerative disorder characterized by the selective loss of upper and lower motor neurons, resulting in severe atrophy of muscles and death. Although the exact pathogenic mechanism of mutant superoxide dismutase 1 (SOD1) causing familial ALS is still elusive, toxic protein aggregation leading to insufficiency of chaperones is one of the main hypotheses. In this study, we investigated the effect of over-expressing one of these chaperones, heat shock protein 27 (Hsp27), in ALS. Mice over-expressing the human, mutant SOD1(G93A) were crossed with mice that ubiquitously over-expressed human Hsp27. Even though the single transgenic hHsp27 mice showed protection against spinal cord ischemia, the double transgenic SOD1(G93A)/hHsp27 mice did not live longer, and did not show a significant delay in the onset of disease compared to their SOD1(G93A) littermates. There was no protective effect of hHsp27 over-expression on the motor neurons and on the mutant SOD1 aggregates in the double transgenic SOD1(G93A)/hHsp27 mice. In conclusion, despite the protective action against acute motor neuron injury, Hsp27 alone is not sufficient to protect against the chronic motor neuron injury due to the presence of mutant SOD1.
Krishnan
Jyothsna
J
Laboratory of Neurobiology, Campus Gasthuisberg, Leuven, Belgium.
Vannuvel
Kayleen
K
Andries
Maria
M
Waelkens
Etienne
E
Robberecht
Wim
W
Van Den Bosch
Ludo
L
D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D002470:Cell Survival / Q000235:genetics; D003433:Crosses, Genetic; D019610:Cytoprotection / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008136:Longevity / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1