Pyridine-2,3-dicarboxylate, quinolinic acid, induces 1N4R Tau amyloid aggregation in vitro: Another evidence for the detrimental effect of the inescapable endogenous neurotoxin

Esmaeili, Sajjad; Ghobadi, Nazanin; Akbari, Vali; Moradi, Sajad; Shahlaie, Mohsen; Ghobadi, Sirous; Jalalvand, Alí R.; Amani, Mojtaba; Khodarahmi, Reza

doi:10.1016/j.cbi.2019.108884

Cited by 17 publications

(9 citation statements)

References 80 publications

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“…To obtain the sigmoid curve, the data collected from ThT fluorescence measurements at 485 nm were fitted by the following equation [53]:…”

Section: Thioflavin T (Tht) Fluorescence Assaymentioning

confidence: 99%

Experimental and Theoretical Studies on the Anti-Amyloidogenic and Destabilizing Effects of Pyrogallol Against Human Insulin Protein

Shouhani¹,

Bahramikia²,

Hejazi³

2022

Preprint

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One of the major problems caused by repeated subcutaneous insulin injections in diabetic patients is insulin amyloidosis. Understanding the molecular mechanism of amyloid fibril formation of insulin and finding effective compounds to its inhibit or eliminate is very important and extensive research has been done on it. In this study, the anti-amyloidogenic and destabilizing effects of the pyrogallol, as a phenolic compound, on human insulin protein were investigated by CR absorbance, ThT and ANS fluorescence, FTIR spectroscopy and atomic force microscopy. According to the obtained results, the formation of amyloid fibrils at pH 2.0 and 50 °C was confirmed by CR, ThT, ANS, FTIR assays. Microscopic images also showed the twisted and long structures of amyloid fibrils. Simultaneous incubation of the protein with pyrogallol at different concentrations reduced the intensities of CR, ThT and ANS in a dose-dependent manner and no trace of fibrillar structures was observed in the microscopic images. FTIR spectroscopy also showed that the position of amide I band in the spectrum of samples containing pyrogallol was shifted. Based on the findings in this study, it can be concluded that pyrogallol can be effective in preventing and suppressing human insulin amyloid fibrils.

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“…To obtain the sigmoid curve, the data collected from ThT fluorescence measurements at 485 nm were fitted by the following equation [53]:…”

Section: Thioflavin T (Tht) Fluorescence Assaymentioning

confidence: 99%

Experimental and Theoretical Studies on the Anti-Amyloidogenic and Destabilizing Effects of Pyrogallol Against Human Insulin Protein

Shouhani¹,

Bahramikia²,

Hejazi³

2022

Preprint

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show abstract

“…To obtain the sigmoid curve, the data collected from ThT fluorescence measurements at 485 nm were fitted by the following equation (Esmaeili et al, 2020):…”

Section: Thioflavin T (Tht) Fluorescence Assaymentioning

confidence: 99%

Experimental and theoretical studies on the anti‐amyloidogenic and destabilizing effects of pyrogallol against human insulin protein

Shouhani

Bahramikia

Hejazi

2022

Journal of Food Biochemistry

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One of the major problems caused by repeated subcutaneous insulin injections in diabetic patients is insulin amyloidosis. Understanding the molecular mechanism of amyloid bril formation of insulin and nding effective compounds to its inhibit or eliminate is very important and extensive research has been done on it. In this study, the anti-amyloidogenic and destabilizing effects of the pyrogallol, as a phenolic compound, on human insulin protein were investigated by CR absorbance, ThT and ANS uorescence, FTIR spectroscopy and atomic force microscopy. According to the obtained results, the formation of amyloid brils at pH 2.0 and 50°C was con rmed by CR, ThT, ANS, FTIR assays. Microscopic images also showed the twisted and long structures of amyloid brils. Simultaneous incubation of the protein with pyrogallol at different concentrations reduced the intensities of CR, ThT and ANS in a dose-dependent manner and no trace of brillar structures was observed in the microscopic images. FTIR spectroscopy also showed that the position of amide I band in the spectrum of samples containing pyrogallol was shifted. Based on the ndings in this study, it can be concluded that pyrogallol can be effective in preventing and suppressing human insulin amyloid brils. Supplementary FilesThis is a list of supplementary les associated with this preprint. Click to download.

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“…Its neurotoxicity is higher than 3-HK. The acknowledged mechanisms of QUIN-mediated cytotoxicity have been studied [ 116 ]. QUIN is a selective agonist of N-methyl-D-aspartate (NMDA) receptor.…”

Section: Endogenous Neurotoxinsmentioning

confidence: 99%

“…QUIN inhibits mitochondrial complexes, leading to energy deficiency and apoptosis. Recently, it was proposed that QUIN accelerates amyloid oligomerization of 1N4R Tau in vitro, which is associated with AD [ 116 ]. This is another adverse factor of QUIN as an endogenous neurotoxin.…”

Section: Endogenous Neurotoxinsmentioning

confidence: 99%

Neurotoxicity and Underlying Mechanisms of Endogenous Neurotoxins

Cao

Ismail

et al. 2021

IJMS

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Endogenous and exogenous neurotoxins are important factors leading to neurodegenerative diseases. In the 1980s, the discovery that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) contributes to Parkinson’s disease (PD) symptoms led to new research investigations on neurotoxins. An abnormal metabolism of endogenous substances, such as condensation of bioamines with endogenous aldehydes, dopamine (DA) oxidation, and kynurenine pathway, can produce endogenous neurotoxins. Neurotoxins may damage the nervous system by inhibiting mitochondrial activity, increasing oxidative stress, increasing neuroinflammation, and up-regulating proteins related to cell death. This paper reviews the biological synthesis of various known endogenous neurotoxins and their toxic mechanisms.

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Pyridine-2,3-dicarboxylate, quinolinic acid, induces 1N4R Tau amyloid aggregation in vitro: Another evidence for the detrimental effect of the inescapable endogenous neurotoxin

Cited by 17 publications

References 80 publications

Experimental and Theoretical Studies on the Anti-Amyloidogenic and Destabilizing Effects of Pyrogallol Against Human Insulin Protein

Experimental and Theoretical Studies on the Anti-Amyloidogenic and Destabilizing Effects of Pyrogallol Against Human Insulin Protein

Experimental and theoretical studies on the anti‐amyloidogenic and destabilizing effects of pyrogallol against human insulin protein

Neurotoxicity and Underlying Mechanisms of Endogenous Neurotoxins

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