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Decrease of Hsp25 protein expression precedes degeneration of motoneurons in ALS‐SOD1 mice
Author(s) -
Maatkamp Arjen,
Vlug Angela,
Haasdijk Elize,
Troost Dirk,
French Pim J.,
Jaarsma Dick
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2004.03430.x
Subject(s) - sod1 , western blot , heat shock protein , biology , amyotrophic lateral sclerosis , blot , messenger rna , motor neuron , immunocytochemistry , in situ hybridization , microbiology and biotechnology , mutant , neuroscience , medicine , endocrinology , gene , biochemistry , spinal cord , disease
We have investigated the expression of Hsp25, a heat shock protein constitutively expressed in motoneurons, in amyotrophic lateral sclerosis (ALS) mice that express G93A mutant SOD1 (G93A mice). Immunocytochemistry and Western blotting showed that a decrease of Hsp25 protein expression occurred in motoneurons of G93A mice prior to the onset of motoneuron death and muscle weakness. This decrease in Hsp25 expression also preceded the appearance of SOD1 aggregates as identified by cellulose acetate filtration and Western blot analysis. In contrast to Hsp25 protein levels, Hsp25 mRNA as determined by in situ hybridization and RT‐PCR, remained unchanged. This suggests that the decrease in Hsp25 protein levels occurs post‐transcriptionally. In view of the cytoprotective properties of Hsp25 and the temporal relationship between decreased Hsp25 expression and the onset of motoneuron death, it is feasible that reduced Hsp25 concentration contributes to the degeneration of motoneurons in G93A mice. These data are consistent with the idea that mutant SOD1 may reduce the availability of the protein quality control machinery in motoneurons.