2017
DOI: 10.1074/jbc.m116.757179
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Phosphorylation at Ser8 as an Intrinsic Regulatory Switch to Regulate the Morphologies and Structures of Alzheimer's 40-residue β-Amyloid (Aβ40) Fibrils

Abstract: Polymorphism of amyloid-β (Aβ) fibrils, implying different fibril structures, may play important pathological roles in Alzheimer's disease (AD). Morphologies of Aβ fibrils were found to be sensitive to fibrillation conditions. Herein, the Ser-phosphorylated Aβ (pAβ), which is assumed to specially associate with symptomatic AD, is reported to modify the morphology, biophysical properties, cellular toxicity, and structures of Aβ fibrils. Under the same fibrillation conditions, pAβ favors the formation of fibrils… Show more

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Cited by 32 publications
(42 citation statements)
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References 79 publications
(147 reference statements)
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“…For CB [8] group, CB [8] could not reduce the cytotoxicity of Ab 1-40 fibrils whereas it rescued the cytotoxicity of Ab 4-40 fibrils significantly (Figure 6B). These observations werec onsistent with our fibril-end binding based inhibition mechanism, since far less toxic maturef ibrils [26,27] would be formedi nt he presence of CBs. It should be noted that CB [7] and CB [8] showedn ot oxic or nutrient effect on N2A cells ( Figure S9, Supporting Information).…”
Section: Resultssupporting
confidence: 86%
See 1 more Smart Citation
“…For CB [8] group, CB [8] could not reduce the cytotoxicity of Ab 1-40 fibrils whereas it rescued the cytotoxicity of Ab 4-40 fibrils significantly (Figure 6B). These observations werec onsistent with our fibril-end binding based inhibition mechanism, since far less toxic maturef ibrils [26,27] would be formedi nt he presence of CBs. It should be noted that CB [7] and CB [8] showedn ot oxic or nutrient effect on N2A cells ( Figure S9, Supporting Information).…”
Section: Resultssupporting
confidence: 86%
“…In this study,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on N2A cell line was conducted. [26] For CB [7] group,C B [7] could rescue the cytotoxicity of both fibrils. Yett he cell viability for Ab 4-40 group on 1:10 and 1:50 ratio was much higher ( Figure 6A).…”
Section: Resultsmentioning
confidence: 96%
“…the English (His6Arg) and the Tottori (Asp7His) mutant, which show accelerated fibril formation [13, 14]. Phosphorylation of Ser8 significantly changes the fibril topology [15], whereas a Ser8Cys mutation favors the formation of soluble dimers by oxidative crosslinking [16, 17]. Metal ions like Zn 2+ bind to N-terminal residues and accelerate amyloid formation [1820].…”
Section: Introductionmentioning
confidence: 99%
“…The membrane channel hypothesis for AD thus provides an explanation why antiparallel Aβ42 oligomers are more toxic and detrimental than other forms of Aβ 13,14 . Findings that some Aβ42 oligomers have an antiparallel β secondary structure that is similar to that of OMPA (an antiparallel β-barrel channel) 13 , that antibodies to Aβ42 oligomers also recognize some toxins that form antiparallel β-barrel transmembrane channels 15,16 , and that the Iowa mutant that leads to early onset AD also causes some fibrils to adopt an antiparallel β structure 6 support our hypothesis 17,18 that Aβ42 oligomers, annular protofibrils, and channels possess concentric antiparallel β-barrels.…”
Section: Introductionmentioning
confidence: 63%