beta-Amyloid protein aggregation: its implication in the physiopathology of Alzheimer's disease.
beta-Amyloid protein (A beta), a 39-42 residue peptide resulting from the proteolytic processing of a membrane-bound beta-amyloid precursor protein (APP), is one of the major components of the fibrillar deposits observed in Alzheimer patients. A beta fibril formation is a complex process which involves changes in A beta conformation and self-association to form cross-beta pleated sheets, protofibrils, and fibrils. Since the aggregation of soluble A beta peptide into fibrils is viewed as a critical event in the physiopathology of Alzheimer's disease (AD), preventing, altering, or reversing fibril formation may thus be of therapeutic value. This review will focus on the current state of knowledge of A beta fibril formation, with special emphasis on physiological and exogenous inhibitors which may have a therapeutic potential.
UFR 927 des Sciences de la Vie, Université Pierre et Marie Curie, 4 Place Jussieu, 75252 Paris.
L
L
Dumery
F
F
Bourdel
Y
Y
Soussan
A
A
Fialkowsky
S
S
Viale
P
P
Nicolas
M
M
Reboud-Ravaux
D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009454:Neurofibrils / Q000737:chemistry; D018384:Oxidative Stress; D011487:Protein Conformation
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010450:Endopeptidases