TY  - JOUR
AU  - Leliveld, S. R.
AU  - Korth, C.
TI  - The use of conformation-specific ligands and assays to dissect the molecular mechanisms of neurodegenerative diseases
JO  - Journal of neuroscience research
VL  - 85
SN  - 0360-4012
CY  - New York, NY [u.a.]
PB  - Wiley-Liss
M1  - PreJuSER-59552
SP  - 2285 - 2297
PY  - 2007
N1  - Record converted from VDB: 12.11.2012
AB  - The use of conformation-specific ligands has been closely linked to progress in the molecular characterization of neurodegenerative diseases. Deposition of misfolded or misprocessed proteins is now recognized as a hallmark of all neurodegenerative diseases. Initially, dyes like Congo red and thioflavin T were used as crudely conformation-specific ligands for staining the beta-sheeted protein components of amyloid deposits in neurodegenerative diseases such as Alzheimer disease (AD) and prion disease, the two diseases in which protein conformations were distinguished early on. This conformational characterization of extracellular protein deposits with dyes ultimately led to the identification of key players in the disease processes. The recent discovery of intermediate conformational species, i.e., soluble oligomers for AD and PK-sensitive PrP(Sc) for prion disease, whose conformation and assembly are thought to be distinct from both the physiological and the fibrillar conformational states, replaced the former notion that the microscopic protein deposits themselves caused disease. This insight and the generation of conformation-specific monoclonal antibodies to these conformers further advanced diagnosis and the understanding of molecular mechanisms of AD and are likely to do so in other neurodegenerative diseases. Here we review how conformer distinction performed by a variety of different techniques, including biophysical, biochemical, and antibody-based methods, led to the current molecular concepts of AD and the prion diseases. We provide an outlook on the application of these techniques in advancing the understanding of molecular mechanisms of other neurodegenerative diseases or degenerative brain conditions.
KW  - Amyloid beta-Peptides: chemistry
KW  - Animals
KW  - Antibodies, Monoclonal
KW  - Brain: pathology
KW  - Brain Chemistry
KW  - Humans
KW  - Ligands
KW  - Neurodegenerative Diseases: diagnosis
KW  - Neurodegenerative Diseases: pathology
KW  - Peptides: chemistry
KW  - PrPSc Proteins: chemistry
KW  - Protein Conformation
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Antibodies, Monoclonal (NLM Chemicals)
KW  - Ligands (NLM Chemicals)
KW  - Peptides (NLM Chemicals)
KW  - PrPSc Proteins (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:17497676
UR  - <Go to ISI:>//WOS:000248971500001
DO  - DOI:10.1002/jnr.21353
UR  - https://juser.fz-juelich.de/record/59552
ER  -