Elucidating amyloid beta-protein folding and assembly: A multidisciplinary approach.
Oligomeric, neurotoxic amyloid protein assemblies are thought to be causative agents in Alzheimer's and other neurodegenerative diseases. Development of oligomer-specific therapeutic agents requires a mechanistic understanding of the oligomerization process. This is a daunting task because amyloidogenic protein oligomers often are metastable and comprise structurally heterogeneous populations in equilibrium with monomers and fibrils. A single methodological approach cannot elucidate the entire protein assembly process. An integrated multidisciplinary program is required. We discuss here the synergistic application of in hydro, in vacuo, and in silico methods to the study of the amyloid beta-protein, the key pathogenetic agent in Alzheimer's disease.
Teplow
David B
DB
Department of Neurology, David Geffen School of Medicine, Brain Research Institute, and Molecular Biology Institute, University of California, Los Angeles, California 90095, USA. dteplow@ucla.edu
Lazo
Noel D
ND
Bitan
Gal
G
Bernstein
Summer
S
Wyttenbach
Thomas
T
Bowers
Michael T
MT
Baumketner
Andrij
A
Shea
Joan-Emma
JE
Urbanc
Brigita
B
Cruz
Luis
L
Borreguero
Jose
J
Stanley
H Eugene
HE
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D013816:Thermodynamics
D016229:Amyloid beta-Peptides