% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Schlenzig:6518,
      author       = {Schlenzig, D. and Manhart, S. and Cinar, Y. and Willbold,
                      D. and Funke, S. A. and Kleinschmidt, M. and Hause, G. and
                      Schilling, S. and Demuth, H.-U.},
      title        = {{P}yroglutamate formation influences solubility and
                      amyloidogenicity of amyloid peptides. {A} driving force in
                      different neurodegenerative disorders?},
      journal      = {Biochemistry},
      volume       = {48},
      issn         = {0006-2960},
      address      = {Columbus, Ohio},
      publisher    = {American Chemical Society},
      reportid     = {PreJuSER-6518},
      pages        = {7072 - 7078},
      year         = {2009},
      note         = {Record converted from VDB: 12.11.2012},
      abstract     = {N-Terminally truncated and pyroglutamate (pGlu) modified
                      amyloid beta (Abeta) peptides are major constituents of
                      amyloid deposits in sporadic and inherited Alzheimer's
                      disease (AD). Formation of pGlu at the N-terminus confers
                      resistance against cleavage by most aminopeptidases,
                      increases toxicity of the peptides, and may seed Abeta
                      aggregate formation. Similarly, the deposited amyloid
                      peptides ABri and ADan, which cause a very similar
                      histopathology in familial British dementia (FBD) and
                      familial Danish dementia (FDD), are N-terminally blocked by
                      pGlu. Triggered by the coincidence of pGlu-modified amyloid
                      peptides and similar pathology in AD, FBD, and FDD, we
                      investigated the impact of N-terminal pGlu on biochemical
                      and biophysical properties of Abeta, ABri, and ADan.
                      N-Terminal pGlu increases the hydrophobicity and changes the
                      pH-dependent solubility profile, rendering the pGlu-modified
                      peptides less soluble in the basic pH range. The pGlu
                      residue increases the aggregation propensity of all amyloid
                      peptides as evidenced by ThT fluorescence assays and dynamic
                      light scattering. The far-UV CD spectroscopic analysis
                      points toward an enhanced beta-sheet structure of the
                      pGlu-Abeta. Importantly, changes in fibril morphology are
                      clearly caused by the N-terminal pGlu, resulting in the
                      formation of short fibers, which are frequently arranged in
                      bundles. The effect of pGlu on the morphology is virtually
                      indistinguishable between ABri, ADan, and Abeta. The data
                      provide evidence for a comparable influence of the pGlu
                      modification on the aggregation process of structurally
                      different amyloid peptides, thus likely contributing to the
                      molecularly distinct neurodegenerative diseases AD, FBD, and
                      FDD. The main driving force for the aggregation is
                      apparently an increase in the hydrophobicity and thus an
                      accelerated seed formation.},
      keywords     = {Alzheimer Disease: metabolism / Amino Acid Sequence /
                      Amyloid: chemistry / Amyloid: metabolism / Amyloid:
                      ultrastructure / Circular Dichroism / Humans / Hydrogen-Ion
                      Concentration / Microscopy, Electron / Molecular Sequence
                      Data / Peptides: chemistry / Peptides: metabolism /
                      Pyrrolidonecarboxylic Acid: metabolism / Solubility /
                      Spectrophotometry, Ultraviolet / Amyloid (NLM Chemicals) /
                      Peptides (NLM Chemicals) / Pyrrolidonecarboxylic Acid (NLM
                      Chemicals) / J (WoSType)},
      cin          = {ISB-3 / JARA-HPC},
      ddc          = {570},
      cid          = {I:(DE-Juel1)VDB942 / $I:(DE-82)080012_20140620$},
      pnm          = {Funktion und Dysfunktion des Nervensystems},
      pid          = {G:(DE-Juel1)FUEK409},
      shelfmark    = {Biochemistry $\&$ Molecular Biology},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:19518051},
      UT           = {WOS:000268175600035},
      doi          = {10.1021/bi900818a},
      url          = {https://juser.fz-juelich.de/record/6518},
}