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- W4310102484 abstract "Transient soluble oligomers of amyloid-β (Aβ) are toxic and accumulate early prior to insoluble plaque formation and cognitive impairment in Alzheimer’s disease (AD). Synthetic cyclic D,L-α-peptides (e.g., 1 ) self-assemble into cross β-sheet nanotubes, react with early Aβ species (1-3 mers), and inhibit Aβ aggregation and toxicity in stoichiometric concentrations, in vitro. Employing a semicarbazide as an aza-glycine residue with an extra hydrogen-bond donor to tune nanotube assembly and amyloid engagement, [azaGly 6 ]- 1 inhibited Aβ aggregation and toxicity at substoichiometric concentrations. High-resolution NMR studies revealed dynamic interactions between [azaGly 6 ]- 1 and Aβ42 residues F19 and F20, which are pivotal for early dimerization and aggregation. In an AD mouse model, brain positron emission tomography (PET) imaging using stable 64 Cu-labeled (aza)peptide tracers gave unprecedented early amyloid detection in 44-d presymptomatic animals. No tracer accumulation was detected in the cortex and hippocampus of 44-d-old 5xFAD mice; instead, intense PET signal was observed in the thalamus, from where Aβ oligomers may spread to other brain parts with disease progression. Compared with standard 11 C-labeled Pittsburgh compound-B ( 11 C-PIB), which binds specifically fibrillar Aβ plaques, 64 Cu-labeled (aza)peptide gave superior contrast and uptake in young mouse brain correlating with Aβ oligomer levels. Effectively crossing the blood–brain barrier (BBB), peptide 1 and [azaGly 6 ]- 1 reduced Aβ oligomer levels, prolonged lifespan of AD transgenic Caenorhabditis elegans , and abated memory and behavioral deficits in nematode and murine AD models. Cyclic (aza)peptides offer novel promise for early AD diagnosis and therapy." @default.
- W4310102484 created "2022-11-30" @default.
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- W4310102484 date "2022-11-28" @default.
- W4310102484 modified "2023-10-14" @default.
- W4310102484 title "Early diagnosis and treatment of Alzheimer’s disease by targeting toxic soluble Aβ oligomers" @default.
- W4310102484 cites W1677883125 @default.
- W4310102484 cites W1964543086 @default.
- W4310102484 cites W1975595547 @default.
- W4310102484 cites W1977002082 @default.
- W4310102484 cites W1978746207 @default.
- W4310102484 cites W1980825524 @default.
- W4310102484 cites W1989948422 @default.
- W4310102484 cites W1993190737 @default.
- W4310102484 cites W1995272223 @default.
- W4310102484 cites W2000770097 @default.
- W4310102484 cites W2007236469 @default.
- W4310102484 cites W2011982570 @default.
- W4310102484 cites W2017508122 @default.
- W4310102484 cites W2031231661 @default.
- W4310102484 cites W2039706105 @default.
- W4310102484 cites W2050868331 @default.
- W4310102484 cites W2063571630 @default.
- W4310102484 cites W2068601978 @default.
- W4310102484 cites W2070837551 @default.
- W4310102484 cites W2073809598 @default.
- W4310102484 cites W2074994510 @default.
- W4310102484 cites W2075481535 @default.
- W4310102484 cites W2077267667 @default.
- W4310102484 cites W2078212921 @default.
- W4310102484 cites W2078504128 @default.
- W4310102484 cites W2082429191 @default.
- W4310102484 cites W2093861673 @default.
- W4310102484 cites W2094476178 @default.
- W4310102484 cites W2096410114 @default.
- W4310102484 cites W2117537971 @default.
- W4310102484 cites W2120717592 @default.
- W4310102484 cites W2121753059 @default.
- W4310102484 cites W2121963977 @default.
- W4310102484 cites W2132154794 @default.
- W4310102484 cites W2142038032 @default.
- W4310102484 cites W2147083367 @default.
- W4310102484 cites W2152222652 @default.
- W4310102484 cites W2165021720 @default.
- W4310102484 cites W2165186407 @default.
- W4310102484 cites W2170644095 @default.
- W4310102484 cites W2202388976 @default.
- W4310102484 cites W2221305104 @default.
- W4310102484 cites W2229673765 @default.
- W4310102484 cites W2233646922 @default.
- W4310102484 cites W2256555384 @default.
- W4310102484 cites W2274785614 @default.
- W4310102484 cites W2313989869 @default.
- W4310102484 cites W2460536069 @default.
- W4310102484 cites W2507898423 @default.
- W4310102484 cites W2510806376 @default.
- W4310102484 cites W2769095960 @default.
- W4310102484 cites W2786084903 @default.
- W4310102484 cites W2791343562 @default.
- W4310102484 cites W2792144047 @default.
- W4310102484 cites W2802272643 @default.
- W4310102484 cites W2803581690 @default.
- W4310102484 cites W2809078375 @default.
- W4310102484 cites W2903753579 @default.
- W4310102484 cites W2908547452 @default.
- W4310102484 cites W2914848043 @default.
- W4310102484 cites W2941088151 @default.
- W4310102484 cites W2943665787 @default.
- W4310102484 cites W2946968312 @default.
- W4310102484 cites W2954682095 @default.
- W4310102484 cites W2984827280 @default.
- W4310102484 cites W2999548695 @default.
- W4310102484 cites W3037182986 @default.
- W4310102484 cites W3044090667 @default.
- W4310102484 cites W3083205846 @default.
- W4310102484 cites W3092235588 @default.
- W4310102484 cites W3101507523 @default.
- W4310102484 cites W3110489045 @default.
- W4310102484 cites W3129110576 @default.
- W4310102484 cites W3130915146 @default.
- W4310102484 cites W3131910442 @default.
- W4310102484 cites W3137826907 @default.
- W4310102484 cites W3152692563 @default.
- W4310102484 cites W3164476032 @default.
- W4310102484 cites W3173953727 @default.
- W4310102484 cites W3176983361 @default.