Dual Functional Small Molecule Probes as Fluorophore and Ligand for Misfolding Proteins

Zhang, Xueli; Ran, Chongzhao

doi:10.2174/1385272811317060004

Cited by 28 publications

(21 citation statements)

References 117 publications

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“…This structure was introduced because it is half of Chrysamine-G, which is a very close analog of Congo red, one of the most used compounds for staining Aβ plaques in brain slices [55] . The double bond in stilbene is the bridge connecting the electron donor and acceptor.…”

Section: Derivatives Of Stilbenementioning

confidence: 99%

Advances in development of fluorescent probes for detecting amyloid-β aggregates

Ren

Tang

et al. 2016

Acta Pharmacol Sin

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With accumulating evidence suggesting that amyloid-β (Aβ) deposition is a good diagnostic biomarker for Alzheimer's disease (AD), the discovery of active Aβ probes has become an active area of research. Among the existing imaging methods, optical imaging targeting Aβ aggregates (fibrils or oligomers), especially using near-infrared (NIR) fluorescent probes, is increasingly recognized as a promising approach for the early diagnosis of AD due to its real time detection, low cost, lack of radioactive exposure and high-resolution. In the past decade, a variety of fluorescent probes have been developed and tested for efficiency in vitro, and several probes have shown efficacy in AD transgenic mice. This review classifies these representative probes based on their chemical structures and functional modes (dominant solvent-dependent mode and a novel solvent-independent mode). Moreover, the pharmaceutical characteristics of these representative probes are summarized and discussed. This review provides important perspectives for the future development of novel NIR Aβ diagnostic probes.

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Section: Derivatives Of Stilbenementioning

confidence: 99%

Advances in development of fluorescent probes for detecting amyloid-β aggregates

Ren

Tang

et al. 2016

Acta Pharmacol Sin

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“…We hypothesise here that the 'dense matted deposits' seen earlier are in fact β-rich amyloids, and that it is this coagulopathy in particular that contributes significantly to the procession of sepsis along or through the cascade of toxicity outlined in Fig 1. In particular, thioflavin T (ThT) is a stain whose fluorescence (when excited at 440-450nm or so) is massively enhanced upon binding to β-rich amyloids (e.g. [126][127][128][129][130][131][132][133][134][135]) . Fig 3 A,B show SEM pictures of 'normal' clots and dense matted deposits, respectively, while Fig 3C,D show how ThT stains clotted platelet-poor plasma from a patient with an inflammatory disease (type 2 diabetes) much more strongly than the equivalent plasma from a healthy control.…”

Section: Amyloid-like Conformational Transitions In Fibrin(ogen)mentioning

confidence: 99%

To what extent are the terminal stages of sepsis, septic shock, SIRS, and multiple organ dysfunction syndrome actually driven by a prion/amyloid form of fibrin?

Kell

Pretorius

2016

Preprint

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A well-established development of increasing disease severity leads from sepsis through septic shock, SIRS, multiple organ dysfunction syndrome and cellular and organismal death. We argue that a chief culprit is the LPS-induced anomalous coagulation of fibrinogen to produce a form of fibrin that is at once inflammatory, resistant to fibrinolysis, and underpins the disseminated intravascular coagulation commonly observed in sepsis. In particular, we argue that the form of fibrin produced is anomalous because much of its normal α-helical content is transformed to β-sheets, as occurs in established amyloidogenic and prion diseases. We hypothesise that these processes play a major role in the passage along the above pathways to organismal death, and that inhibiting them would be of great therapeutic value, a claim for which there is emerging evidence.

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“…The thioflavin stains (based on a thiazole nucleus) probably count most nearly as "God's gift to students of amyloid and amyloidogenesis". Free thioflavin T (ThT) fluoresces faintly with excitation and emission maxima of 350 and 440 nm, respectively, whereas upon interaction with amyloid fibrils a substantially enhanced ThT fluorescence is observed, with excitation and emission maxima at about 440/450 and 480/490 nm, respectively [188][189][190][191][192][193][194][195][196][197][198][199][200][201][202][203][204]. Table 2 summarises the wavelengths used in a number of studies.…”

Section: Thioflavin S Thioflavin T and Derivativesmentioning

confidence: 99%

Substoichiometric molecular control and amplification of the initiation and nature of amyloid fibril formation: lessons from and for blood clotting

Pretorius

2016

Preprint

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The chief and largely terminal element of normal blood clotting is considered to involve the polymerisation of the mainly α-helical fibrinogen to fibrin, with a binding mechanism involving ‘knobs and holes’ but with otherwise littl change in protein secondary structure. We recognise, however, that extremely unusual mutations, or mechanical stressing, can cause fibrinogen to adopt a conformation containing extensive β-sheets. Similarly, prions can change morphology from a largely alpha-helical to a largely β-sheet conformation, and the latter catalyses both the transition and the self-organising polymerisation of the β-sheet structures. Many other proteins can do this, where it is known as amyloidogenesis. When fibrin is formed in samples from patients harbouring different diseases it can have widely varying diameters and morphologies. We here develop the idea, and summarise the evidence, that in many cases the anomalous fibrin fibre formation seen in such diseases actually amounts to amyloidogenesis. In particular, fibrin can interact withthe amyloid-β (Aβ) protein that is misfolded in Alzheimer's disease. Seeing these unusual fibrin morphologies as true amyloids explains a great deal about fibrin(ogen) biology that was previously opaque, and provides novel strategies for treating such coagulopathies. The literature on blood clotting can usefully both inform and be informed by that on prions and on the many other widely recognised (β)-amyloid proteins.“Novel but physiologically important factors that affect fibrinolysis have seldom been discovered and characterized in recent years” [1]

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Dual Functional Small Molecule Probes as Fluorophore and Ligand for Misfolding Proteins

Cited by 28 publications

References 117 publications

Advances in development of fluorescent probes for detecting amyloid-β aggregates

Advances in development of fluorescent probes for detecting amyloid-β aggregates

To what extent are the terminal stages of sepsis, septic shock, SIRS, and multiple organ dysfunction syndrome actually driven by a prion/amyloid form of fibrin?

Substoichiometric molecular control and amplification of the initiation and nature of amyloid fibril formation: lessons from and for blood clotting

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