The antidepressant drug; trazodone inhibits Tau amyloidogenesis: Prospects for prophylaxis and treatment of AD

Akbari, Vali; Ghobadi, Sirous; Mohammadi, Soheila; Khodarahmi, Reza

doi:10.1016/j.abb.2019.108218

Cited by 22 publications

(10 citation statements)

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“…Many studies have shown that psychoactive substances can cause the phosphorylation of tau protein, and tau protein is closely associated with cognitive function. Both suggested that phosphorylated tau is involved in psychoactive substancesrelated CDs [211,212]. We summarized and proposed a potential mechanism of psychoactive substances induced CDs in Fig.…”

Section: Perspectivementioning

confidence: 97%

Mechanism of psychoactive substance-induced cognitive disorders: does tau protein play a role?

Wang¹,

Lv²,

He³

et al. 2022

Front. Biosci. (Landmark Ed)

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Psychoactive substances are a class of chemical substances which could cause public health threats. Cognitive disorders are a category of mental health disorders that primarily affect cognitive abilities. Tau protein could maintain neuronal cytoskeleton stabilization. Post-translational modification of tau, especially phosphorylation, is an important way to regulate the structure and function of tau and phosphorylated tau is closely related to cognitive function. Lots of studies have reported the phenomenon that psychoactive substances can cause cognitive function impairment. We reviewed recent related studies and discussed them by drug classification. We mainly focused on cognitive disorders caused by acute or chronic exposure of each drugs, animal experiments and the mechanisms associated with tau phosphorylation, then compared the similarities and differences among them, trying to find out the common rules. The results suggested that tau phosphorylation is involved in psychoactive substance-induced cognitive disorder and different psychoactive substances may act by affecting amount or activity of different kinases and phosphatases in the metabolic pathway of tau. We demonstrated that tau protein is a potential target for psychoactive substances induced cognitive disorder treatments.

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Section: Perspectivementioning

confidence: 97%

Mechanism of psychoactive substance-induced cognitive disorders: does tau protein play a role?

Wang¹,

Lv²,

He³

et al. 2022

Front. Biosci. (Landmark Ed)

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“…the study drug enhanced reactive oxygen species (ROS) fluorescence, malondialdehyde (MDA), and oxidized glutathione (GSSG) concentration, as well as decreased reduced glutathione (GSH) level and mitochondrial membrane potential (Taziki et al, 2013) rat hepatocytes exposed to a trazodone solution (450 µM) trazodone decreased GSH concentration and increased MDA level (Najibi et al, 2016) in vitro thioflavin T-based fluorimetric assay of trazodone solutions (10, 30, and 50 μM); SHSY5Y cells induced to tau aggregation treated with a trazodone solution (50 μM), evaluated via flow cytometry trazodone at 50 μM inhibited tau fibers generation by almost 40%; the drug nearly completely reduced intracellular oligomerization of tau (Akbari et al, 2020) in vivo studies lipopolysaccharide (LPS)-treated rats exposed to trazodone intravenous administration (1 mg/kg) trazodone reduced cerebral lipid peroxidation and MDA levels, but did not scavenge peroxyl radicals or prevent hyperglycemia (Shen et al, 2005) rats with LPS-induced endotoxin shock pretreated intravenously with trazodone (1 mg/kg) the drug lowered the concentration of nitric oxide (•NO) in plasma as well as inducible nitric oxide synthase (iNOS) in lymphocytes, but not in the aorta and the liver (Shen et al, 2007) male albino mice exposed to trazodone (5 mg/kg and 10 mg/kg) 30 minutes before a forced swim test trazodone dose-dependently diminished concentrations of MDA and nitrite in the brain, and elevated cerebral levels of GSH and catalase (CAT) activity (Kumar et al, 2008) ischemia/reperfusion damage in the brain of Laca mice after trazodone administration (5 and 10 mg/kg) the study drug reduced MDA and nitrite levels, boosted the activity of CAT, superoxide dismutase (SOD) and glutathione-S-transferase (GST), as well as augmented glutathione redox ratio (GSH/GSSG) (A. rats treated with trazodone (5, 10, and 20 mg/kg) and then systemically administrated 3nitropropionic acid trazodone prevented GSH/GSSG decrease as well as mitochondrial complex enzyme impairment in the hippocampus caused by 3-NP (Kumar et al, 2011; male Wistar rats administered trazodone orally to induce testicular injury the drug potentiated MDA level and suppressed the content of total thiols (TTs) as well as CAT activity male albino rats administrated trazodone orally (200 mg/kg/day) trazodone increased MDA concentration and decreased TTs fluorescence as well as CAT activity Antiradical and Antioxidant Activity Excess ROS and reactive nitrogen species (RNS) lead to oxidative stress. Oxidative stress is exacerbated by accumulation of redox-active metals (such as iron).…”

Section: Systematic Reviewmentioning

confidence: 99%

Biochemical and Biophysical in Vitro Studies and Systematic Literature Review on the Antioxidant and Antiglycation Activities of Trazodone

Nesterowicz

Żendzian-Piotrowska

Ładny

et al. 2023

Cell Physiol Biochem

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Background/Aims: Trazodone is a selective serotonin reuptake inhibitor; however, other mechanisms of the drug’s anti-depressive properties have also been postulated. Hence, the aim of the study was to perform a systematic review and assess antiglycoxidative properties of trazodone in in vitro models. Methods: Trazodone’s scavenging and chelating properties were measured with spectrophotometric method. The impact of the drug on carbonyl/oxidative stress was marked in the bovine serum albumin (BSA) model where sugars (glucose, fructose, galactose, ribose) and aldehydes (glyoxal and methylglyoxal) were used as glycation agents. Aminoguanidine and N-acetylcysteine (NAC) were applied as reference glycation/free radical inhibitors. Glycation biomarkers (kynurenine, N-formylkynurenine, dityrosine as well as advanced glycation end products contents) were assessed spectrofluorometrically. Concentrations of oxidation parameters (total thiols (TTs), protein carbonyls (PCs) and also advanced oxidation protein products (AOPPs) levels) were determined spectrophotometrically. Results: We demonstrated that trazodone poorly scavenged radicals (hydroxyl radical, nitric oxide, hydrogen peroxide and 2,2-diphenyl-1-picrylhydrazyl radical) and showed low ferrous ion chelating, unlike aminoguanidine and NAC. Sugars/aldehydes caused enhancement of glycation parameters, as well as a decrease of TTs and an increase of PCs and AOPPs levels compared to BSA incubated alone. Trazodone did not reduce oxidation parameters to the baseline (BSA) and significantly exacerbated glycation markers in comparison with both BSA and BSA+glycators. The content of glycation products was markedly lower in aminoguanidine and NAC than in trazodone. The molecular docking of trazodone to BSA revealed its very low affinity, which may indicate non-specific binding of trazodone, facilitating the attachment of glycation factors. Conclusion: According to our findings, it may be concluded that trazodone poorly counteracts oxidation and intensifies glycation in vitro . A possible mechanism for antiglycoxidative effect of trazodone in vivo may be the enhancement of the body’s adaptive response, as indicated by the results of our systematic review.

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“…An antidepressant drug Trazodone, 1,2,4-triazolo[4,3-a]pyridine derivative, was first reported in 1968 and has been used commonly for the treatment of depression (Figure 8) [271]. In addition to its antidepressant effect, it was recently reported that trazodone inhibits tau amyloidogenesis [272].…”

Section: Triazolopyridinesmentioning

confidence: 99%

Fused Pyridine Derivatives: Synthesis and Biological Activities

Istanbullu¹,

Bayraktar²,

Saylam³

2023

Exploring Chemistry With Pyridine Derivatives

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Five-membered heteroaromatic ring fused pyridine derivatives are of increasing interest in drug design and medicinal chemistry. The structural similarity of many drugs (especially antiviral and anticancer ones) with DNA bases such as adenine and guanine is a key factor to explain their effectiveness. Apart from these, it is also found in the structures of substances with antituberculosis, antibacterial, antifungal, anti-inflammatory, and antimalarial activities. Another advantage of this group of compounds is their positive contribution to solubility, polarity, lipophilicity, and hydrogen bonding capacity properties of the compounds they are incorporated into. In this chapter, various bioactivities of fused pyridine derivatives will be categorized and summarized.

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The antidepressant drug; trazodone inhibits Tau amyloidogenesis: Prospects for prophylaxis and treatment of AD

Cited by 22 publications

References 100 publications

Mechanism of psychoactive substance-induced cognitive disorders: does tau protein play a role?

Mechanism of psychoactive substance-induced cognitive disorders: does tau protein play a role?

Biochemical and Biophysical in Vitro Studies and Systematic Literature Review on the Antioxidant and Antiglycation Activities of Trazodone

Fused Pyridine Derivatives: Synthesis and Biological Activities

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