Amyloid-beta: acute-phase apolipoprotein with metal-binding activity.
In monomeric form, amyloid-beta (Abeta), an amphipatic 4 kDa peptide which plays a key role in the pathogenesis of Alzheimer's disease (AD), is associated with lipoproteins in biological fluids and possesses high affinity to transition metal ions; in addition, synthesis of Abeta is upregulated under acute phase conditions. These data suggest that Abeta can be regarded as a normal physiological component of lipoproteins and may represent an acute-phase apolipoprotein with metal-binding activity. Interaction with transition metal ions may cause aggregation of Abeta, leading to formation of oligomers. Such oligomerised Abeta may lose its normal biological functions and acquire deleterious activities. To be efficient, novel anti-AD therapies should target oligomeric forms of Abeta while preserving the monomeric form of the peptide.
Kontush
Anatol
A
INSERM Unité 551, Hôpital de la Pitié, Pavillon Benjamin Delessert, 83, Bd de l'Hôpital, 75651 Paris Cedex 13, France. kontush@chups.jussieu.fr
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001053:Apolipoproteins / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000503:physiopathology; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D007477:Ions; D008670:Metals / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D028561:Transition Elements
D000209:Acute-Phase Proteins; D016229:Amyloid beta-Peptides; D001053:Apolipoproteins; D002352:Carrier Proteins; D007477:Ions; D008670:Metals; D028561:Transition Elements