Lipid membranes and beta-amyloid: a harmful connection.
Gradual changes in steady-state levels of beta amyloid peptides (Abeta) in the brain are considered as initial step in the amyloid cascade hypothesis of Alzheimer's disease (AD). Abeta is a product of the secretase cleavage of the amyloid precursor protein and there is evidence that the membrane lipid environment may modulate secretase activity and alters its function. Abeta disturbs membrane properties of artificial and isolated biological membranes and of plasma membranes in living cells. Abeta induced changes in membrane fluidity could be explained by physico-chemical interactions of the peptide with membrane components such as cholesterol, phospholipids and gangliosides. Thus, cell membranes may be the location where the neurotoxic cascade of Abeta is initiated. Perturbation of membranes, binding to lipids and alteration of cellular calcium signaling by Abeta have been reported by several studies and these topics are examined in this review.
Eckert
G P
GP
Goethe-University of Frankfurt, Department of Pharmacology,Campus Riedberg, Biocenter N260 R1.09, Max-von-Laue Strasse 9, D-60438 Frankfurt, Germany. G.P.Eckert@em.uni-frankfurt.de
Wood
W G
WG
Müller
W E
WE
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D008051:Lipid Bilayers; D005677:G(M1) Ganglioside; D002784:Cholesterol