Biological surfaces as catalysts of amyloid aggregate nucleation and primary sites of amyloid toxicity.
The themes of protein folding, misfolding, aggregation and aggregate toxicity to living systems are among the most exciting frontiers in molecular and cell biology as well as in molecular medicine. This is testified by the increasingly higher number of publications on these issues and the debate in the scientific community about some basic questions still unresolved. One of the latter is the role performed in vitro by synthetic and in vivo by biological surfaces in favouring or disfavouring protein folding and misfolding, in speeding the rate of aggregate nucleation and as key targets of toxic aggregates. Indeed, recent research has highlighted the roles of surfaces in all these phenomena; it has also stressed that early oligomeric assemblies in the path of fibrillization are endowed with the highest cytotoxicity and that the latter most likely follows aggregate interaction with cell membrane(s). The resulting membrane destabilization and permeabilization with early alterations in intracellular redox status and ion homeostasis possibly culminates with cell death. Each of these steps is most likely influenced by the physicochemical and biochemical features of the membrane(s) themselves in ways that are still under investigation. This review summarizes the most recent advances in these fields.
Stefani
Massimo
M
Department of Biochemical Sciences, Research Centre on the Molecular Basis of Neurodegeneration, University of Florence, Florence, Italy. stefani@scibio.unifi.it
D000682:Amyloid / Q000737:chemistry* / Q000633:toxicity; D000686:Amyloidosis / Q000503:physiopathology*; D002462:Cell Membrane / Q000502:physiology; D006801:Humans; D008563:Membrane Lipids / Q000502:physiology; D008566:Membranes / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D011487:Protein Conformation; D017510:Protein Folding; D020836:Protein Structure, Quaternary
D000682:Amyloid; D008563:Membrane Lipids