Search: (L773:1437 4331) srt2:(2000-2004) >
Amyloid :
Amyloid : Morphology and Toxicity
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- Olofsson, A. (author)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Östman, Johan (author)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Lundgren, E. (author)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten)
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(creator_code:org_t)
- 2002
- 2002
- English.
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In: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 40:12, s. 1266-1270
- Related links:
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https://urn.kb.se/re...
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Abstract
Subject headings
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- We have expressed transthyretin (TTR) mutants which have significantly destabilised tetramers that aggregate into amyloid fibrils via a series of intermediates. We used atomic force microscopy to follow the morphology of aggregates during fibril formation. Initially, amorphous aggregates are formed that subsequently mature into fibrillar structures. This observation is interpreted as an optimisation of beta-strand registers. The rate of aggregation and maturation is highly temperature-dependent suggesting that entropic forces significantly contribute to stability. In addition, we identified a correlation between the presence of early formed aggregates of TTR and cytotoxicity. The toxic response was mediated via an apoptotic mechanism. The fact that early formed amorphous aggregates, but not more mature fibrils, exert a toxic response suggests that the rate of fibril formation may be a critical parameter. We propose that a slow rate of aggregation facilitates an increased concentration of a toxic intermediate.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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