Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in Alzheimer’s disease brains

Anumala, Upendra Rao; Gu, Jiamin; Monte, Fabio Lo; Krämer, Thomas; Haußen, Roland Heyny-von; Hölzer, Jana; Goetschy-Meyer, Valérie; Schön, Christian; Mall, Gerhard; Hilger, Ingrid; Czech, Christian; Herms, Jochen; Schmidt, Boris

doi:10.1016/j.bmc.2013.06.039

Cited by 16 publications

(14 citation statements)

References 29 publications

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“…They are non-toxic either in HepG2 cells and in zebrafish embryos at high concentrations. Interestingly, their preference for NFT vs. Ab plaque staining is not predicted by in vitro aggregation assays, where 6.37c is almost equipotent (inhibition at low nM concentration) on tau and Ab [258].…”

Section: Interfering With (Neuro)toxic Tau Species In the Aggregationmentioning

confidence: 70%

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Targeting Assembly and Disassembly of Protein Aggregates

Seneci

2015

Chemical Modulators of Protein Misfolding and Neurodegenerative Disease

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Section: Interfering With (Neuro)toxic Tau Species In the Aggregationmentioning

confidence: 70%

“…administration [257]. Fluorescent rhodanine-based imaging agents such as 6.37c are NFT-selective staining agents in post-mortem samples from the brains of AD patients [258]. They are non-toxic either in HepG2 cells and in zebrafish embryos at high concentrations.…”

Section: Interfering With (Neuro)toxic Tau Species In the Aggregationmentioning

confidence: 99%

Targeting Assembly and Disassembly of Protein Aggregates

Seneci

2015

Chemical Modulators of Protein Misfolding and Neurodegenerative Disease

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“…The data provides a solid base for further investigations of their applicability to image-based detection of AD in vivo (Bolander et al 2012). Moreover, a series of rhodanine-3-acetic acids was synthesized and shown to bind to neurofibrillary tangles with a comparably high binding affinity (e.g., IC50 = 19 nM) (Anumala et al 2013). Lastly, trimethine cyanine dyes bind to tau fibrils (Gu et al 2013).…”

Section: Imaging Of Infectionsmentioning

confidence: 98%

Small Animal Imaging

2017

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“…Phenotypic screens, particularly in CNS drug discovery, have been markedly more efficient in identifying novel therapeutic entities than target-based assays in recent pre-clinical studies (1999–2008) (Swinney and Anthony, 2011). Zebrafish embryos have also been used to study the potential toxicity of an imaging probe for NFTs (Anumala et al, 2013) and a neuroprotective agent for AD (Torres et al, 2014).…”

Section: Zebrafish For Drug Discovery In Tauopathiesmentioning

confidence: 99%

Heparan Sulfate as a Therapeutic Target in Tauopathies: Insights From Zebrafish

Soussi-Yanicostas

2018

Front. Cell Dev. Biol.

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Microtubule-associated protein tau (MAPT) hyperphosphorylation and aggregation, are two hallmarks of a family of neurodegenerative disorders collectively referred to as tauopathies. In many tauopathies, including Alzheimer’s disease (AD), progressive supranuclear palsy (PSP) and Pick’s disease, tau aggregates are found associated with highly sulfated polysaccharides known as heparan sulfates (HSs). In AD, amyloid beta (Aβ) peptide aggregates associated with HS are also characteristic of disease. Heparin, an HS analog, promotes misfolding, hyperphosphorylation and aggregation of tau protein in vitro. HS also provides cell surface receptors for attachment and uptake of tau seeds, enabling their propagation. These findings point to HS-tau interactions as potential therapeutic targets in tauopathies. The zebrafish genome contains genes paralogous to MAPT, genes orthologous to HS biosynthetic and chain modifier enzymes, and other genes implicated in AD. The nervous system in the zebrafish bears anatomical and chemical similarities to that in humans. These homologies, together with numerous technical advantages, make zebrafish a valuable model for investigating basic mechanisms in tauopathies and identifying therapeutic targets. Here, we comprehensively review current knowledge on the role of HSs in tau pathology and HS-targeting therapeutic approaches. We also discuss novel insights from zebrafish suggesting a role for HS 3-O-sulfated motifs in tau pathology and establishing HS antagonists as potential preventive agents or therapies for tauopathies.

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Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in Alzheimer’s disease brains

Cited by 16 publications

References 29 publications

Targeting Assembly and Disassembly of Protein Aggregates

Targeting Assembly and Disassembly of Protein Aggregates

Small Animal Imaging

Heparan Sulfate as a Therapeutic Target in Tauopathies: Insights From Zebrafish

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