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Cystatin C reduces the in vitro formation of soluble A beta 1-42 oligomers and protofibrils

Selenica, M. L.; Wang, Xin LU ; Ostergaard-Pedersen, L.; Westlind-Danielsson, A. and Grubb, Anders LU (2007) In Scandinavian Journal of Clinical & Laboratory Investigation 67(2). p.179-190
Abstract
There are an increasing number of genetic and neuropathological observations to suggest that cystatin C, an extracellular protein produced by all nucleated cells, might play a role in the pathophysiology of sporadic Alzheimer's disease (AD). Recent observations indicate that small and large soluble oligomers of the beta-amyloid protein (A beta) impair synaptic plasticity and induce neurotoxicity in AD. The objective of the present study was to investigate the influence of cystatin C on the production of such oligomers in vitro. Co-incubation of cystatin C with monomeric A beta 1-42 significantly attenuated the in vitro formation of A beta oligomers and protofibrils, as determined using electron microscopy (EM), dodecyl sulphate... (More)
There are an increasing number of genetic and neuropathological observations to suggest that cystatin C, an extracellular protein produced by all nucleated cells, might play a role in the pathophysiology of sporadic Alzheimer's disease (AD). Recent observations indicate that small and large soluble oligomers of the beta-amyloid protein (A beta) impair synaptic plasticity and induce neurotoxicity in AD. The objective of the present study was to investigate the influence of cystatin C on the production of such oligomers in vitro. Co-incubation of cystatin C with monomeric A beta 1-42 significantly attenuated the in vitro formation of A beta oligomers and protofibrils, as determined using electron microscopy (EM), dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, thioflavin T (ThT) spectrofluorimetry and gel chromatography. However, cystatin C did not dissolve preformed A beta oligomers. Direct binding of cystatin C to A beta was demonstrated with the formation of an initial 1:1 molar high-affinity complex. These observations suggest that cystatin C might be a regulating element in the transformation of monomeric A beta to larger and perhaps more toxic molecular species in vivo. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cysteine protease, beta amyloid protein, ADDLs, Alzheimer's disease, inhibitor
in
Scandinavian Journal of Clinical & Laboratory Investigation
volume
67
issue
2
pages
179 - 190
publisher
Informa Healthcare
external identifiers
  • wos:000244842400008
  • scopus:33947133671
ISSN
1502-7686
DOI
10.1080/00365510601009738
language
English
LU publication?
yes
id
8386e901-ae22-4e7a-b2ec-ded7e80e5f7f (old id 665304)
date added to LUP
2007-12-18 09:48:03
date last changed
2017-07-30 04:38:50
@article{8386e901-ae22-4e7a-b2ec-ded7e80e5f7f,
  abstract     = {There are an increasing number of genetic and neuropathological observations to suggest that cystatin C, an extracellular protein produced by all nucleated cells, might play a role in the pathophysiology of sporadic Alzheimer's disease (AD). Recent observations indicate that small and large soluble oligomers of the beta-amyloid protein (A beta) impair synaptic plasticity and induce neurotoxicity in AD. The objective of the present study was to investigate the influence of cystatin C on the production of such oligomers in vitro. Co-incubation of cystatin C with monomeric A beta 1-42 significantly attenuated the in vitro formation of A beta oligomers and protofibrils, as determined using electron microscopy (EM), dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, thioflavin T (ThT) spectrofluorimetry and gel chromatography. However, cystatin C did not dissolve preformed A beta oligomers. Direct binding of cystatin C to A beta was demonstrated with the formation of an initial 1:1 molar high-affinity complex. These observations suggest that cystatin C might be a regulating element in the transformation of monomeric A beta to larger and perhaps more toxic molecular species in vivo.},
  author       = {Selenica, M. L. and Wang, Xin and Ostergaard-Pedersen, L. and Westlind-Danielsson, A. and Grubb, Anders},
  issn         = {1502-7686},
  keyword      = {cysteine protease,beta amyloid protein,ADDLs,Alzheimer's disease,inhibitor},
  language     = {eng},
  number       = {2},
  pages        = {179--190},
  publisher    = {Informa Healthcare},
  series       = {Scandinavian Journal of Clinical & Laboratory Investigation},
  title        = {Cystatin C reduces the in vitro formation of soluble A beta 1-42 oligomers and protofibrils},
  url          = {http://dx.doi.org/10.1080/00365510601009738},
  volume       = {67},
  year         = {2007},
}