2018
DOI: 10.1186/s40035-018-0111-2
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Surfen and oxalyl surfen decrease tau hyperphosphorylation and mitigate neuron deficits in vivo in a zebrafish model of tauopathy

Abstract: BackgroundTauopathies comprise a family of neurodegenerative disorders including Alzheimer’s disease for which there is an urgent and unmet need for disease-modifying treatments. Tauopathies are characterized by pathological tau hyperphosphorylation, which has been shown to correlate tightly with disease progression and memory loss in patients suffering from Alzheimer’s disease. We recently demonstrated an essential requirement for 3-O-sulfated heparan sulfate in pathological tau hyperphosphorylation in zebraf… Show more

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Cited by 17 publications
(9 citation statements)
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“…For whole mount immunostaining, 5 dpf wild-type embryos with or without microglia, were fixed in 4% formaldehyde in PBS for 1 h 30 min at room temperature, washed three times in PBS (10 min each) and permeabilized in cold acetone (−20°C) for 20 min. After several washes, embryos were incubated in collagenase solution for 1 h. Immunohistochemistry was performed as described previously (Naini et al, 2018) using rabbit anti-zebrafish L-plastin polyclonal antibody (gift of Dr. Michael Redd, University College London, United Kingdom), followed by Alexa-coupled secondary anti-rabbit antibody (Molecular Probes) at 1:500 dilution. After washing, the fluorescence was analyzed using a Leica TCS SP8 confocal scanning system (Leica Microsystems).…”
Section: Methodsmentioning
confidence: 99%
“…For whole mount immunostaining, 5 dpf wild-type embryos with or without microglia, were fixed in 4% formaldehyde in PBS for 1 h 30 min at room temperature, washed three times in PBS (10 min each) and permeabilized in cold acetone (−20°C) for 20 min. After several washes, embryos were incubated in collagenase solution for 1 h. Immunohistochemistry was performed as described previously (Naini et al, 2018) using rabbit anti-zebrafish L-plastin polyclonal antibody (gift of Dr. Michael Redd, University College London, United Kingdom), followed by Alexa-coupled secondary anti-rabbit antibody (Molecular Probes) at 1:500 dilution. After washing, the fluorescence was analyzed using a Leica TCS SP8 confocal scanning system (Leica Microsystems).…”
Section: Methodsmentioning
confidence: 99%
“… 3 , 4 As previously reported, we found that 1% DMSO concentration had no effect on larval development. 5 …”
Section: Resultsmentioning
confidence: 99%
“…Surfen, a non-specific heparan sulfate antagonist interferes with numerous biological processes, showing potential as a therapeutic agent. The properties of surfen ranges from anti-inflammatory (Warford et al, 2018) and immuomodulatory (Warford et al, 2014) to suppression of stem cell differentiation (Huang et al, 2018), inhibition of HIV type 1 infection (Roan et al, 2010) and rescue of tauopathy in a zebrafish model (Alavi Naini et al, 2018). However, non-specificity limits the beneficial effects of surfen.…”
Section: Heparan Sulfate Proteoglycansmentioning
confidence: 99%
“…An additional approach consists of treatment with heparan sulfate antagonist molecules. In a recent proof of concept study a rescue of neuronal abnormalities upon treatment with surfen and oxalyl surfen was observed in the Tg[HuC::hTau P301L /DsRed] zebrafish model (Alavi Naini et al, 2018). Figure 1 summarizes the two approaches in Tg[HuC::hTau P301L /DsRed] zebrafish.…”
Section: Therapeutic Approaches Targeting Hspgs In Tauopathiesmentioning
confidence: 99%
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