A comparison of amyloid fibrillogenesis using the novel fluorescent compound K114.
Proteinaceous inclusions with amyloidogenic properties are a common link between many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Histological and in vitro studies of amyloid fibrils have advanced the understanding of protein aggregation, and provided important insights into pathogenic mechanisms of these neurodegenerative brain amyloidoses. The classical amyloid dyes Congo Red (CR) and thioflavin T and S, have been used extensively to detect amyloid inclusions in situ. These dyes have also been utilized to monitor the maturation of amyloid fibrils assembled from monomer subunits in vitro. Recently, the compound (trans,trans)-1-bromo-2,5-bis-(3- hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB), derived from the structure of CR, was shown to bind to a wide range of amyloid inclusions in situ. More importantly it was also used to label brain amyloids in live animals. Herein, we show that an analogue of BSB, (trans,trans)-1-bromo-2,5-bis-(4-hydroxy)styrylbenzene (K114), recognizes amyloid lesions, and has distinctive properties which allowed the quantitative monitoring of the formation of amyloid fibrils assembled from the amyloid-beta peptide, alpha-synuclein, and tau.
Crystal
Adam S
AS
The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Giasson
Benoit I
BI
Crowe
Alexander
A
Kung
Mei-Ping
MP
Zhuang
Zhi-Ping
ZP
Trojanowski
John Q
JQ
Lee
Virginia M-Y
VM
D000682:Amyloid / Q000032:analysis* / Q000138:chemical synthesis; D003224:Congo Red / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry; D019636:Neurodegenerative Diseases / Q000473:pathology*; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence; D013194:Staining and Labeling / Q000379:methods*; D013343:Styrenes / Q000737:chemistry; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins / Q000737:chemistry
C430896:1-bromo-2,5-bis(3-hydroxycarbonyl-4-hydroxy)styrylbenzene; D000682:Amyloid; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D013343:Styrenes; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins; D003224:Congo Red