Fluorescence as a method to reveal structures and membrane-interactions of amyloidogenic proteins.
Amyloidogenesis is a characteristic feature of the 40 or so known protein deposition diseases, and accumulating evidence strongly suggests that self-association of misfolded proteins into either fibrils, protofibrils, or soluble oligomeric species is cytotoxic. The most likely mechanism for toxicity is through perturbation of membrane structure, leading to increased membrane permeability and eventual cell death. There have been a rather limited number of investigations of the interactions of amyloidogenic polypeptides and their aggregated states with membranes; these are briefly reviewed here. Amyloidogenic proteins discussed include A-beta from Alzheimer's disease, the prion protein, alpha-synuclein from Parkinson's disease, transthyretin (FAP, SSA amyloidosis), immunoglobulin light chains (primary (AL) amyloidosis), serum amyloid A (secondary (AA) amyloidosis), amylin or IAPP (Type 2 diabetes) and apolipoproteins. This review highlights the significant role played by fluorescence techniques in unraveling the nature of amyloid fibrils and their interactions and effects on membranes. Fluorescence spectroscopy is a valuable and versatile method for studying the complex mechanisms of protein aggregation, amyloid fibril formation and the interactions of amyloidogenic proteins with membranes. Commonly used fluorescent techniques include intrinsic and extrinsic fluorophores, fluorescent probes incorporated in the membrane, steady-state and lifetime measurements of fluorescence emission, fluorescence correlation spectroscopy, fluorescence anisotropy and polarization, fluorescence resonance energy transfer (FRET), fluorescence quenching, and fluorescence microscopy.
Munishkina
Larissa A
LA
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
Fink
Anthony L
AL
D000682:Amyloid / Q000032:analysis / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016923:Cell Death; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D002463:Cell Membrane Permeability; D005453:Fluorescence; D005470:Fluorometry / Q000379:methods; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D017510:Protein Folding; D020836:Protein Structure, Quaternary
D000682:Amyloid