2010
DOI: 10.1371/journal.pone.0011101
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Complete Phenotypic Recovery of an Alzheimer's Disease Model by a Quinone-Tryptophan Hybrid Aggregation Inhibitor

Abstract: The rational design of amyloid oligomer inhibitors is yet an unmet drug development need. Previous studies have identified the role of tryptophan in amyloid recognition, association and inhibition. Furthermore, tryptophan was ranked as the residue with highest amyloidogenic propensity. Other studies have demonstrated that quinones, specifically anthraquinones, can serve as aggregation inhibitors probably due to the dipole interaction of the quinonic ring with aromatic recognition sites within the amyloidogenic… Show more

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Cited by 131 publications
(211 citation statements)
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References 63 publications
(72 reference statements)
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“…The metal complexes can specifically bind to the hydrophobic core fragment of Aβ1-40, which was consistent with our above results. In addition, compared with NMR spectrum of Aβ1-40 alone, there were obvious peak shifts in signals from amide protons of K16 (2.95 ppm), and E22 (2.52 ppm) in the presence of Λ2 and Δ2 ( Figure 4B and 4C) 52,53 . The NMR spectrum of the Aβ1-40 in the presence of Λ2 (Figure 4, blue) was different from that treated with Δ2.…”
Section: Esi-msmentioning
confidence: 96%
See 1 more Smart Citation
“…The metal complexes can specifically bind to the hydrophobic core fragment of Aβ1-40, which was consistent with our above results. In addition, compared with NMR spectrum of Aβ1-40 alone, there were obvious peak shifts in signals from amide protons of K16 (2.95 ppm), and E22 (2.52 ppm) in the presence of Λ2 and Δ2 ( Figure 4B and 4C) 52,53 . The NMR spectrum of the Aβ1-40 in the presence of Λ2 (Figure 4, blue) was different from that treated with Δ2.…”
Section: Esi-msmentioning
confidence: 96%
“…The binding sites and different binding models between the chiral metal complexes and Aβ1-40 were further confirmed by NMR spectroscopy [49][50][51][52][53] . The 1 H NMR signals of the aromatic moieties (F19F20) 49,50 of Aβ1-40 underwent remarkably change upon addition of complex 2, revealing their interactions associated with these units (Figure 4A and 4D).…”
Section: Esi-msmentioning
confidence: 99%
“…Mannitol Ameliorates Behavioral Deficits of Drosophila Model of PD-The locomotion (climbing) assay, commonly used for assessing behavior of Drosophila flies expressing amyloidogenic proteins in their brain (31)(32)(33)(34), was used to evaluate the effect of mannitol on a fly model of PD, expressing mutant A53T ␣-syn in their nervous system via the Gal4-UAS system. Although normal flies tend to climb up the side of a tube, A53T ␣-syn-expressing flies remain at the bottom (35).…”
Section: Mannitol Inhibition Of ␣-Syn Fibril Formation As Determinedmentioning
confidence: 99%
“…Large screening campaigns have led to the identification of a variety of compounds that directly interfere with Aß, mHtt and Tau protein misfolding and aggregation in cell-free systems, as well as compounds that modulate the activity of heat-shock proteins and other chaperones [132][133][134][135][136][137][138] (Figure 4). However, for both classes of compounds, the translation of therapeutic efficacy into mouse models has been difficult.…”
Section: Targeting Protein Misfolding Directly And/or Through Chaperonesmentioning
confidence: 99%
“…While early studies focused on preventing the formation of large amyloid aggregates, it is now clear that misfolding events occurring early in the amyloidogenic process lead to the generation of monomers or small oligomers that can mediate neurotoxicity and degradation 142,143 . Due to difficulties in detecting these smaller toxic assemblies, the exact mechanism of action for many aggregation inhibitors such as the benzothiazoles, C2-8 or triazines remains unknown, and while they prevent the formation of large Aß plaques and mHtt aggregates 132,133,136 , they might not interfere with initial misfolding steps and thus not have a significant impact on pathogenesis (Figure 4).…”
Section: Targeting Protein Misfolding Directly And/or Through Chaperonesmentioning
confidence: 99%