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@ARTICLE{Goerke:119332,
author = {S. Goerke$^*$ and K. S. Milde$^*$ and R. Bukowiecki and P.
Kunz$^*$ and K. Klika$^*$ and T. Wiglenda and A. Mogk and E.
E. Wanker and B. Bukau$^*$ and M. Ladd$^*$ and P.
Bachert$^*$ and M. Zaiss$^*$},
title = {{A}ggregation-induced changes in the chemical exchange
saturation transfer ({CEST}) signals of proteins.020},
journal = {NMR in biomedicine},
volume = {30},
number = {1},
issn = {0952-3480},
address = {New York, NY},
publisher = {Wiley},
reportid = {DKFZ-2017-00087},
pages = {e3665 -},
year = {2017},
abstract = {Chemical exchange saturation transfer (CEST) is an MRI
technique that allows mapping of biomolecules (small
metabolites, proteins) with nearly the sensitivity of
conventional water proton MRI. In living organisms, several
tissue-specific CEST effects have been observed and
successfully applied to diagnostic imaging. In these
studies, particularly the signals of proteins showed a
distinct correlation with pathological changes. However, as
CEST effects depend on various properties that determine and
affect the chemical exchange processes, the origins of the
observed signal changes remain to be understood. In this
study, protein aggregation was identified as an additional
process that is encoded in the CEST signals of proteins.
Investigation of distinct proteins that are involved in
pathological disorders, namely amyloid beta and huntingtin,
revealed a significant decrease of all protein CEST signals
upon controlled aggregation. This finding is of particular
interest with regard to diagnostic imaging of patients with
neurodegenerative diseases that involve amyloidogenesis,
such as Alzheimers or Huntingtons disease. To investigate
whether the observed CEST signal decrease also occurs in
heterogeneous mixtures of aggregated cellular proteins, and
thus prospectively in tissue, heat-shocked yeast cell
lysates were employed. Additionally, investigation of
different cell compartments verified the assignment of the
protein CEST signals to the soluble part of the proteome.
The results of in vitro experiments demonstrate that
aggregation affects the CEST signals of proteins. This
observation can enable hypotheses for CEST imaging as a
non-invasive diagnostic tool for monitoring pathological
alterations of the proteome in vivo.},
cin = {E020 / G404 / A250},
ddc = {610},
cid = {I:(DE-He78)E020-20160331 / I:(DE-He78)G404-20160331 /
I:(DE-He78)A250-20160331},
pnm = {315 - Imaging and radiooncology (POF3-315)},
pid = {G:(DE-HGF)POF3-315},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27859838},
doi = {10.1002/nbm.3665},
url = {https://inrepo02.dkfz.de/record/119332},
}