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BRICHOS binds to a ...
BRICHOS binds to a designed amyloid-forming beta-protein and reduces proteasomal inhibition and aggresome formation
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- Johansson, Jan (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Karolinska Institute,Tallinn University
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- Presto, Jenny (author)
- Karolinska Institute
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(creator_code:org_t)
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- 2016
- 2016
- English.
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In: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 473, s. 167-178
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Abstract
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- The BRICHOS domain is associated with proliferative, degenerative and amyloid diseases, and it has been shown to inhibit fibril formation and toxicity of the Alzheimer's disease-associated amyloid beta-peptide. ProSP-C (prosurfactant protein C) BRICHOS binds to stretches of hydrophobic amino acid residues, which are unfolded or in beta-strand conformation, suggesting that it may have broad anti-amyloid activity. We have studied the effect of the proSP-C BRICHOS domain on the designed amyloidogenic beta-sheet proteins beta 17 and beta 23. beta 17 expressed in the secretory pathway of HEK (human embryonic kidney)-293 cells forms intracellular inclusions, whereas beta 23 is rapidly degraded. Co-expression of BRICHOS leads to a reduction in beta 17 inclusion size and increased levels of soluble beta 17 and beta 23. Furthermore, BRICHOS interacts with the beta-proteins intracellularly, reduces their ubiquitination and decreases aggresome formation and proteasomal inhibition. Collectively, these data suggest that BRICHOS is capable of delaying the aggregation process and toxicity of amyloidogenic proteins in a generic manner.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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