Amyloid proteins oligomerization

Ginkgo s inhibitory effect on the production of amyloid-beta protein has also been mediated by other mechanisms, such as acetylcholinesterase inhibition, modulation of amyloid protein oligomeric species, and lowering of free cholesterol levels." ... 

Bitan, G Lomakin, A. and Teplow, D. B. (2001) Amyloid beta-protein oligomerization prenucleation interactions revealed by photo-induced cross-linking of unmodified proteins. J. Biol. Chem. 276, 35176-35184. 

Bitan G, Vollers SS, Teplow DB (2003b) Elucidation of primary structure elements controlling early amyloid beta-protein oligomerization. J Biol Chem 278 34882-34889 Blake C, Serpell L (1996) Synchrotron X-ray smdies suggest that the core of the transthyretin amyloid fibril is a continuous beta-sheet heUx. Structure 4 989-998... 

FIGURE 8.6 Pore formation by amyloid proteins a membrane-assisted process. Amyloid proteins that have acquired an a-helical structure upon binding to Kpid rafts can penetrate the membrane. The presence of cholesterol rmderneath the glycosphingoHpids (GSL) in lipid raft areas stimulates both the insertion of the protein within the membrane and its oligomerization into Ca -permeable pores. 

This survey of the intrinsic and environmental factors that govern the oligomerization and aggregation properties of amyloid proteins indicates that lipid rafts exert an important control on these phenomena. Individual cases of lipid-amyloid interactions are discussed in the following chapters. However, at this stage, we should mention that raft lipids... 

Deciphering tiie molecular mechanisms by which lipid rafts interact with amyloid proteins and control their oligomerization/aggregation into neurotoxic superstructures is a prerequisite for developing these new therapeutic strategies. The discovery of strikingly common mechanisms shared by distinct amyloid proteins raises some hope for the discovery of a common cure for all these diseases. 

Urbane, B., Betnel, M., Cruz, L., Bitan, G., 8c Teplow, D. B. (2010). Elucidation of amyloid beta-protein oligomerization mechanisms Discrete molecular dynamics study. Journal of the American Chemical Society, 132, 4266. 

BACE-1 (p-secretase) is one of the enzymes involved in breaking down APP to produce Ap (amyloid p-peptide, Ap40>42), the protein that eventually oligomerizes to form Ap plaques, the hallmark of Alzheimer s disease (AD). Thus an agent that... 

Bitan, G., Kirkitadze, M.D., Lomakin, A., Vollers, S.S., Benedek, G.B., and Teplow, D.B. (2003) Amyloid B-protein (otP) assembly ap40 and ap42 oligomerize through distinct pathways. Proc. Natl. Acad. Sci. USA 100, 330-335. 

These three examples emphasize the idea that a complete description of amyloid fibril polymorphisms will only be achieved when 3D structures at atomic detail become available (Luhrs et al., 2005). Last but not least, since the various morphologies observed for amyloid fibrils are defining the end point of the assembly process, an essential need is to properly define the early stages of fibril formation, namely the oligomeric states of the peptide or protein in solution prior to assembly into fibrils. 

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