Indirubin Derivative 7-Bromoindirubin-3-Oxime (7Bio) Attenuates Aβ Oligomer-Induced Cognitive Impairments in Mice

Li-ping, Chen; Huang, Chunhui; Shentu, Jieyi; Wang, Minjun; Yan, Sicheng; Fei, Zhou; Zhang, Zaijun; Wang, Chuang; Han, Yifan; Wang, Qinwen; Cui, Wei

doi:10.3389/fnmol.2017.00393

Cited by 16 publications

(15 citation statements)

References 41 publications

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“…Like most diseases, PD is modulated by various environmental and genetic factors. Genetic mutations including the mutation in A53T Synuclein [ 3 ] and environmental factors such as sedentary lifestyle, exposure to certain insecticides, neurotoxins, MPTP, 6-OHDA, rotenone and paraquat might induce PD [ 2 , 4 ]. MPTP is a lipid soluble substance, able to cross the blood-brain barrier, oxidized by the glial enzyme Monoamine oxidase B to a toxic agent called 1-methyl-4-phenylpyridinium-4-methyl-1 (MPP + ) [ [4] , [5] , [6] ].…”

Section: Introductionmentioning

confidence: 99%

Altered expression of miR-29a-3p and miR-34a-5p by specific inhibition of GSK3β in the MPP+ treated SH-SY5Y Parkinson's model

Ahmadzadeh-Darinsoo

Abbasi

Arefian

et al. 2022

Non-coding RNA Research

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In the current study, the effects of 7-BIO as a specific GSK3β inhibitor was examined on cell survival and expression of miR-29a-3p and miR-34a-5p in neurotoxin MPP + treated SH-SY5Y cells. Our findings revealed that while co-treatment of the cells with 7-BIO and MPP + did not alter the toxicity induced by MPP + , pretreatment with 3.5 μM 7-BIO for 6 h increased the survival of the 2 mM MPP + treated cells. Also, qRT-PCR analysis of gene expression showed that while miR-29a-3p was unchanged in cells treated with either 2 mM MPP + or 3.5 μM 7-BIO alone, miR-34a-5p was increased by MPP + but decreased by 7-BIO. Pretreatment with 3.5 μM 7-BIO prior to MPP + however, increased miR-29a-3p but decreased miR-34a-5p induced by MPP + . We therefore suggest that 7-BIO inhibition of GSK3β alleviates the MPP + induced neurotoxicity by regulating miR-29a-3p and miR-34a-5p expressions in Parkinson's disease model SH-SY5Y cells.

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Section: Introductionmentioning

confidence: 99%

Altered expression of miR-29a-3p and miR-34a-5p by specific inhibition of GSK3β in the MPP+ treated SH-SY5Y Parkinson's model

Ahmadzadeh-Darinsoo

Abbasi

Arefian

et al. 2022

Non-coding RNA Research

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“…Aβ oligomer preparation was described in previous studies reported by us [27][28][29]. Brie y, Aβ peptide was dissolved in hexa uoroisopropanol (HFIP, Aladdin, Shanghai, China) to form Aβ monomers.…”

Section: Preparation Of Aβ Oligomersmentioning

confidence: 99%

Dimeric Tacrine (10)-Hupyridone Effectively Combats Alzheimer’s Disease as A Multi-Target-Directed Ligand

Xuan

Yan

et al. 2021

Preprint

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Background Alzheimer’s disease (AD) is a neurodegenerative disorder with multiple pathological features. Therefore, multi-target-directed ligands (MTDLs) strategy has been developed to combat this disease. We have previously designed and synthesized dimeric tacrine (10)-hupyridone (A10E), a novel tacrine derivative with acetylcholinesterase (AChE) inhibition and brain-derived neurotrophic factor (BDNF) activation activity, by linking tacrine and a fragment of huperzine A. However, it was largely unknown whether A10E could act on other AD targets and produce cognition-enhancing ability in AD animal models. Methods Behavioral and biochemical methods were applied to evaluate multi-target cognitive-enhancing effects and mechanisms of A10E in APP/PS1 transgenic mice and β-amyloid (Aβ) oligomers-treated mice. The neuroprotective mechanisms of A10E were explored in SH-SY5Y cells. And the anti-aggregation effects of A10E on Aβ were directly investigated in vitro. Results A10E could prevent cognitive impairments in both APP/PS1 mice and Aβ oligomers-treated mice, with higher potency than tacrine and huperzine A. Moreover, A10E could effectively inhibit Aβ production and deposition, reduce neuroinflammation, enhance brain derived brain-derived neurotrophic factor (BDNF) expression, and elevate cholinergic neurotransmission in vivo. A10E, at nanomolar concentrations, could also inhibit Aβ oligomers-induced neurotoxicity via the activation of the TrkB/Akt pathway. Furthermore, Aβ oligomerization and fibrillization could be directly disrupted by A10E. Conclusion A10E could produce anti-AD neuroprotective effects via multi-target mechanisms, including the inhibition of Aβ aggregation, the activation of the BDNF/TrkB pathway, the reduction of neuroinflammation and the decrease of AChE activity. As MTDLs could produce additional benefits, such as overcoming the deficits of drug combination and enhancing the compliance of AD patients, our results suggested that A10E might be developed as a promising MTDL lead for the treatment of AD.

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“…. The NORT were conducted in an open-field arena (30 × 30 × 30 cm) constructed with polyvinyl chloride, plywood, and acrylic as previously described [26]. The tasks included a training session and a recognition session for two consecutive days.…”

Section: Novel Object Recognition Test (Nort)mentioning

confidence: 99%

Magnolol Ameliorates Behavioral Impairments and Neuropathology in a Transgenic Mouse Model of Alzheimer’s Disease

Xian

Liu

et al. 2020

Oxidative Medicine and Cellular Longevity

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Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by progressive memory loss. Magnolol (MN), the main active ingredient of Magnolia officinalis, possesses anti-AD effects in several experimental models of AD. In this study, we aimed to explore whether MN could ameliorate the cognitive deficits in TgCRND8 transgenic mice and to elucidate its molecular mechanisms. Male TgCRND8 mice were orally administered with MN (20 and 40 mg/kg) daily for 4 consecutive months, followed by assessing the spatial learning and memory functions using the open-field, radial arm maze, and novel object recognition tests. The results demonstrated that MN (20 and 40 mg/kg) could markedly ameliorate the cognitive deficits in TgCRND8 mice. In addition, MN significantly increased the expression of postsynaptic density protein 93 (PSD93), PSD-95, synapsin-1, synaptotagmin-1, synaptophysin (SYN), and interleukin-10 (IL-10), while markedly reduced the protein levels of tumor necrosis factor alpha (TNF-α), IL-6, IL-1β, Aβ40, and Aβ42, and modulated the amyloid precursor protein (APP) processing and phosphorylation. Immunofluorescence showed that MN significantly suppressed the activation of microglia (Iba-1) and astrocytes (GFAP) in the hippocampus and cerebral cortex of TgCRND8 mice. Mechanistic studies revealed that MN could significantly increase the ratios of p-GSK-3β (Ser9)/GSK-3β, p-Akt (Ser473)/Akt, and p-NF-κB p65/NF-κB p65. These findings indicate that MN exerted cognitive deficits improving effects via suppressing neuroinflammation, amyloid pathology, and synaptic dysfunction through regulating the PI3K/Akt/GSK-3β and NF-κB pathways, suggesting that MN is a promising naturally occurring polyphenol worthy of further developing into a therapeutic agent for AD treatment.

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Indirubin Derivative 7-Bromoindirubin-3-Oxime (7Bio) Attenuates Aβ Oligomer-Induced Cognitive Impairments in Mice

Cited by 16 publications

References 41 publications

Altered expression of miR-29a-3p and miR-34a-5p by specific inhibition of GSK3β in the MPP+ treated SH-SY5Y Parkinson's model

Altered expression of miR-29a-3p and miR-34a-5p by specific inhibition of GSK3β in the MPP+ treated SH-SY5Y Parkinson's model

Dimeric Tacrine (10)-Hupyridone Effectively Combats Alzheimer’s Disease as A Multi-Target-Directed Ligand

Magnolol Ameliorates Behavioral Impairments and Neuropathology in a Transgenic Mouse Model of Alzheimer’s Disease

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