Myelin basic protein binds to and inhibits the fibrillar assembly of Abeta42 in vitro.
The deposition of amyloid beta-protein (Abeta) fibrils into plaques within the brain parenchyma and along cerebral blood vessels is a hallmark of Alzheimer's disease. Abeta peptides are produced through the successive cleavage of the Abeta precursor protein by beta- and gamma-secretase, producing peptides between 39 and 43 amino acids in length. The most common of these are Abeta40 (the most abundant) and Abeta42. Abeta42 is more fibrillogenic than Abeta40 and has been implicated in early Abeta plaque deposition. Our previous studies determined that myelin basic protein (MBP) was capable of inhibiting fibril formation of a highly fibrillogenic Abeta peptide containing both E22Q (Dutch) and D23N (Iowa) mutations associated with familial forms of cerebral amyloid angiopathy [Hoos, M. D., et al. (2007) J. Biol. Chem. 282, 9952-9961]. In this study, we show through a combination of biochemical and ultrastructural techniques that MBP is also capable of inhibiting the beta-sheet fibrillar assembly of the normal Abeta42 peptide. These findings suggest that MBP may play a role in regulating the deposition of Abeta42 and thereby also may regulate the early formation of amyloid plaques in Alzheimer's disease.
Hoos
Michael D
MD
Department of Medicine, Stony Brook University, Stony Brook, New York 11794-8153, USA.
Ahmed
Mahiuddin
M
Smith
Steven O
SO
Van Nostrand
William E
WE
D000544:Alzheimer Disease / Q000378:metabolism; D019943:Amino Acid Substitution / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D004676:Myelin Basic Protein / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D017433:Protein Structure, Secondary / Q000235:genetics
D016229:Amyloid beta-Peptides; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)