Alzheimer's disease: soluble oligomeric Abeta(1-40) peptide in membrane mimic environment from solution NMR and circular dichroism studies.
Amyloid beta peptide (Abeta) is a small peptide present in normal cells and aggregated Abeta is the main constituent of the extracellular amyloid plaques found in Alzheimer's disease (AD) brain. Recent studies suggest that soluble Abeta oligomers are neurotoxic rather than amyloid fibrils found in amyloid plaques. This study using multidimensional NMR spectroscopy and circular dichroism (CD) provides the first direct evidence that alterations in membrane structure can trigger the conversion of soluble alpha-helical monomeric Abeta into oligomeric Abeta in a beta-sheet conformation.
Mandal
Pravat K
PK
Neurophysics Laboratory, Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Pettegrew
Jay W
JW
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008566:Membranes / Q000737:chemistry; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012996:Solutions
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012996:Solutions; C078592:amyloid beta-protein (1-40)