Decrease of Hsp25 protein expression precedes degeneration of motoneurons in ALS‐SOD1 mice

Maatkamp, Arjen; Vlug, Angela S.; Haasdijk, Elize D.; Troost, Dirk; French, Pim J.; Jaarsma, Dick

doi:10.1111/j.1460-9568.2004.03430.x

Cited by 85 publications

(63 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2B). HSP25 levels were increased, probably reflecting the increased expression in astrocytes as previously reported (62,82,89). There was also a slight increase in the levels of HSP90 in the mutant SOD1 mice (Fig.…”

Section: The Inhibition Of Chaperone Activity In Spinal Cord Is Due Tsupporting

confidence: 67%

“…Mutations in two small heat shock proteins, HSP27 and HSP22, cause degeneration of motor axons in humans (63,64). Interestingly, HSP25, a mouse homologue of HSP27, appears to be selectively decreased in motor neurons in mutant SOD1 transgenic mice (89). Overexpression of chaperone HSP70 protects cultured motor neurons from mutant SOD1 toxicity (38).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of Chaperone Activity Is a Shared Property of Several Cu,Zn-Superoxide Dismutase Mutants That Cause Amyotrophic Lateral Sclerosis

Tummala

Jung

Tiwari

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron degeneration, paralysis, and death. Mutant Cu,Znsuperoxide dismutase (SOD1) causes a subset of ALS by an unidentified toxic property. Increasing evidence suggests that chaperone dysfunction plays a role in motor neuron degeneration in ALS. To investigate the relationship between mutant SOD1 expression and chaperone dysfunction, we measured chaperone function in central nervous system tissue lysates from normal mice and transgenic mice expressing human SOD1 variants. We observed a significant decrease in chaperone activity in tissues from mice expressing ALS-linked mutant SOD1 but not control mice expressing human wild type SOD1. This decrease was detected only in the spinal cord, became apparent by 60 days of age (before the onset of muscle weakness and significant motor neuron loss), and persisted throughout the late stages. In addition, this impairment of chaperone activity occurred only in cytosolic but not in mitochondrial and nuclear fractions. Furthermore, multiple recombinant human SOD1 mutants with differing biochemical and biophysical properties inhibited chaperone function in a cell-free extract of normal mouse spinal cords. Thus, mutant SOD1 proteins may impair chaperone function independent of gene expression in vivo, and this inhibition may be a shared property of ALS-linked mutant SOD1 proteins.

show abstract

Section: The Inhibition Of Chaperone Activity In Spinal Cord Is Due Tsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Inhibition of Chaperone Activity Is a Shared Property of Several Cu,Zn-Superoxide Dismutase Mutants That Cause Amyotrophic Lateral Sclerosis

Tummala

Jung

Tiwari

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…2). Similarly, depleted chaperone levels were observed in aggregate-forming mouse models of Huntington disease 39 and amyotrophic lateral sclerosis, 40 and chaperone overexpression successfully suppressed aggregate generation. 41,42 In contrast, Hsp25 was up-regulated, particularly in DDC-refed mice.…”

Section: Discussionmentioning

confidence: 99%

“Toxic memory” via chaperone modification is a potential mechanism for rapid mallory-denk body reinduction

Strnad¹,

Guo²,

So³

et al. 2008

Hepatology

View full text Add to dashboard Cite

The cytoplasmic hepatocyte inclusions, Mallory-Denk bodies (MDBs), are characteristic of several liver disorders, including alcoholic and nonalcoholic steatohepatitis. In mice, MDBs can be induced by long-term feeding with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 3 to 4 months or rapidly reformed in DDC-induced then recovered mice by DDC refeeding or exposure to a wide range of toxins for only 5 to 7 days. The molecular basis for such a rapid reinduction of MDBs is unknown. We hypothesized that protein changes retained after DDC priming contribute to the rapid MDB reappearance and associate with MDB formation in general terms. Two-dimensional differential-in-gel-electrophoresis coupled with mass spectrometry were used to characterize protein changes in livers from the various treatment groups. The alterations were assessed by real-time reverse-transcription polymerase chain reaction and confirmed by immunoblotting. DDC treatment led to pronounced charged isoform changes in several chaperone families, including Hsp25, 60, 70, GRP58, GRP75, and GRP78, which lasted at least for 1 month after discontinuation of DDC feeding, whereas changes in other proteins normalized during recovery. DDC feeding also resulted in altered expression of Hsp72, GRP75, and Hsp25 and in functional impairment of Hsp60 and Hsp70 as determined using a protein complex formation and release assay. The priming toward rapid MDB reinduction lasts for at least 3 months after DDC discontinuation, but becomes weaker after prolonged recovery. MDB reinduction parallels the rapid increase in p62 and Hsp25 levels as well as keratin 8 cross-linking that is normally associated with MDB formation. Conclusion: Persistent posttranslational modifications in chaperone proteins, coupled with protein cross-linking and altered chaperone expression and function likely contribute to the "toxic memory" of DDC-primed mice. We hypothesize that similar changes are important contributors to inclusion body formation in several diseases. (HEPATOLOGY 2008;48:931-942.)

show abstract

“…name) cord [1][2][3] high [4] high [4] UP in neurons [5,6] generally UNCHANGED UP in Purkinje cell (NPD) [7,8] generally UP [9][10][11][12][13][14][15][16] extracellular in AD brain [17] strong [3,18] no [1,19] SOD-1:…”

Section: Introductionmentioning

confidence: 99%

Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders

Carra

Rusmini

Crippa

et al. 2013

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

The family of the mammalian small heat-shock proteins consists of 10 members (sHSPs/HSPBs: HSPB1–HSPB10) that all share a highly conserved C-terminal alpha-crystallin domain, important for the modulation of both their structural and functional properties. HSPB proteins are biochemically classified as molecular chaperones and participate in protein quality control, preventing the aggregation of unfolded or misfolded proteins and/or assisting in their degradation. Thus, several members of the HSPB family have been suggested to be protective in a number of neurodegenerative and neuromuscular diseases that are characterized by protein misfolding. However, the pro-refolding, anti-aggregation or pro-degradative properties of the various members of the HSPB family differ largely, thereby influencing their efficacy and protective functions. Such diversity depends on several factors, including biochemical and physical properties of the unfolded/misfolded client, the expression levels and the subcellular localization of both the chaperone and the client proteins. Furthermore, although some HSPB members are inefficient at inhibiting protein aggregation, they can still exert neuroprotective effects by other, as yet unidentified, manners; e.g. by maintaining the proper cellular redox state or/and by preventing the activation of the apoptotic cascade. Here, we will focus our attention on how the differences in the activities of the HSPB proteins can influence neurodegenerative and neuromuscular disorders characterized by accumulation of aggregate-prone proteins. Understanding their mechanism of action may allow us to target a specific member in a specific cell type/disease for therapeutic purposes.

show abstract

Decrease of Hsp25 protein expression precedes degeneration of motoneurons in ALS‐SOD1 mice

Cited by 85 publications

References 53 publications

Inhibition of Chaperone Activity Is a Shared Property of Several Cu,Zn-Superoxide Dismutase Mutants That Cause Amyotrophic Lateral Sclerosis

Inhibition of Chaperone Activity Is a Shared Property of Several Cu,Zn-Superoxide Dismutase Mutants That Cause Amyotrophic Lateral Sclerosis

“Toxic memory” via chaperone modification is a potential mechanism for rapid mallory-denk body reinduction

Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders

Contact Info

Product

Resources

About