Inducing α-synuclein compaction: a new strategy for inhibiting α-synuclein aggregation?
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摘要
<正>Proteins might misfold during translation and folding or even once they are in their native states, due to stochastic fluctuations, destabilizing mutations or cellular stress. Aberrant protein species are usually detected and either refolded or cleared by the protein quality control machinery(Ciechanover and Kwon, 2015). When misfolded protein conformers
引文
Bartels T,Choi JG,Selkoe DJ(2011)alpha-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation.Nature 477:107-110.
Bertoncini CW,Jung YS,Fernandez CO,Hoyer W,Griesinger C,Jovin TM,Zweckstetter M(2005)Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein.Proc Natl Acad Sci U SA 102:1430-1435.
Bousset L,Pieri L,Ruiz-Arlandis G,Gath J,Jensen PH,Habenstein B,Madiona K,Olieric V,Bockmann A,Meier BH,Melki R(2013)Structural and functional characterization of two alpha-synuclein strains.Nat Commun 4:2575.
Carija A,Pinheiro F,Pujols J,Bras IC,Lazaro DF,Santambrogio C,Grandori R,Outeiro TF,Navarro S,Ventura S(2019)Biasing the native alpha-synuclein conformational ensemble towards compact states abolishes aggregation and neurotoxicity.Redox Biol 22:101135.
Ciechanover A,Kwon YT(2015)Degradation of misfolded proteins in neurodegenerative diseases:therapeutic targets and strategies.Exp Mol Med 47:e147.
Daniels MJ,Nourse JB Jr,Kim H,Sainati V,Schiavina M,Murrali MG,Pan B,Ferrie JJ,Haney CM,Moons R,Gould NS,Natalello A,Grandori R,Sobott F,Petersson EJ,Rhoades E,Pierattelli R,Felli I,Uversky VN,Caldwell KA,et al.(2019)Cyclized NDGA modifies dynamic alpha-synuclein monomers preventing aggregation and toxicity.Sci Rep 9:2937.
Fusco G,De Simone A,Gopinath T,Vostrikov V,Vendruscolo M,Dobson CM,Veglia G(2014)Direct observation of the three regions in alpha-synuclein that determine its membrane-bound behaviour.Nat Commun 5:3827.
Ghosh S,Kundu A,Chattopadhyay K(2018)Small molecules attenuate the interplay between conformational fluctuations,early oligomerization and amyloidosis of alpha synuclein.Sci Rep 8:5481.
Konijnenberg A,Ranica S,Narkiewicz J,Legname G,Grandori R,Sobott F,Natalello A(2016)Opposite Structural effects of epigallocatechin-3-gallate and dopamine binding to alpha-synuclein.Anal Chem 88:8468-8475.
Spillatini MG,Schmidt ML,Lee VM,Trojanowski JQ,Jakes R,Goedert M(1997)Alpha-synuclein in Lewy bodies.Nature 388:839-840.
Tuttle MD,Comellas G,Nieuwkoop AJ,Covell DJ,Berthold DA,Kloepper KD,Courtney JM,Kim JK,Barclay AM,Kendall A,Wan W,Stubbs G,Schwieters CD,Lee VM,George JM,Rienstra CM(2016)Solid-state NMR structure of a pathogenic fibril of full-length human alpha-synuclein.Nat Struct Mol Biol23:409-415.
Uversky VN,Eliezer D(2009)Biophysics of Parkinson’s disease:structure and aggregation of alpha-synuclein.Curr Protein Pept Sci 10:483-499.
Winner B,Jappelli R,Maji SK,Desplats PA,Boyer L,Aigner S,Hetzer C,Loher T,Vilar M,Campioni S,Tzitzilonis C,Soragni A,Jessberger S,Mira H,Consiglio A,Pham E,Masliah E,Gage FH,Riek R(2011)In vivo demonstrastion that alpha-synuclein oligomers are toxic.Proc Natl Acad Sci U S A 108:4194-4199.
Bertoncini CW,Jung YS,Fernandez CO,Hoyer W,Griesinger C,Jovin TM,Zweckstetter M(2005)Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein.Proc Natl Acad Sci U SA 102:1430-1435.
Bousset L,Pieri L,Ruiz-Arlandis G,Gath J,Jensen PH,Habenstein B,Madiona K,Olieric V,Bockmann A,Meier BH,Melki R(2013)Structural and functional characterization of two alpha-synuclein strains.Nat Commun 4:2575.
Carija A,Pinheiro F,Pujols J,Bras IC,Lazaro DF,Santambrogio C,Grandori R,Outeiro TF,Navarro S,Ventura S(2019)Biasing the native alpha-synuclein conformational ensemble towards compact states abolishes aggregation and neurotoxicity.Redox Biol 22:101135.
Ciechanover A,Kwon YT(2015)Degradation of misfolded proteins in neurodegenerative diseases:therapeutic targets and strategies.Exp Mol Med 47:e147.
Daniels MJ,Nourse JB Jr,Kim H,Sainati V,Schiavina M,Murrali MG,Pan B,Ferrie JJ,Haney CM,Moons R,Gould NS,Natalello A,Grandori R,Sobott F,Petersson EJ,Rhoades E,Pierattelli R,Felli I,Uversky VN,Caldwell KA,et al.(2019)Cyclized NDGA modifies dynamic alpha-synuclein monomers preventing aggregation and toxicity.Sci Rep 9:2937.
Fusco G,De Simone A,Gopinath T,Vostrikov V,Vendruscolo M,Dobson CM,Veglia G(2014)Direct observation of the three regions in alpha-synuclein that determine its membrane-bound behaviour.Nat Commun 5:3827.
Ghosh S,Kundu A,Chattopadhyay K(2018)Small molecules attenuate the interplay between conformational fluctuations,early oligomerization and amyloidosis of alpha synuclein.Sci Rep 8:5481.
Konijnenberg A,Ranica S,Narkiewicz J,Legname G,Grandori R,Sobott F,Natalello A(2016)Opposite Structural effects of epigallocatechin-3-gallate and dopamine binding to alpha-synuclein.Anal Chem 88:8468-8475.
Spillatini MG,Schmidt ML,Lee VM,Trojanowski JQ,Jakes R,Goedert M(1997)Alpha-synuclein in Lewy bodies.Nature 388:839-840.
Tuttle MD,Comellas G,Nieuwkoop AJ,Covell DJ,Berthold DA,Kloepper KD,Courtney JM,Kim JK,Barclay AM,Kendall A,Wan W,Stubbs G,Schwieters CD,Lee VM,George JM,Rienstra CM(2016)Solid-state NMR structure of a pathogenic fibril of full-length human alpha-synuclein.Nat Struct Mol Biol23:409-415.
Uversky VN,Eliezer D(2009)Biophysics of Parkinson’s disease:structure and aggregation of alpha-synuclein.Curr Protein Pept Sci 10:483-499.
Winner B,Jappelli R,Maji SK,Desplats PA,Boyer L,Aigner S,Hetzer C,Loher T,Vilar M,Campioni S,Tzitzilonis C,Soragni A,Jessberger S,Mira H,Consiglio A,Pham E,Masliah E,Gage FH,Riek R(2011)In vivo demonstrastion that alpha-synuclein oligomers are toxic.Proc Natl Acad Sci U S A 108:4194-4199.