Hypoxic-conditioned medium from adipose tissue mesenchymal stem cells improved neuroinflammation through alternation of toll like receptor (TLR) 2 and TLR4 expression in model of Alzheimer's disease rats

Mehrabadi, Shima; Motevaseli, Elahe; Sadr, Seyed Shahabeddin; Moradbeygi, Khadijeh

doi:10.1016/j.bbr.2019.112362

Cited by 33 publications

(18 citation statements)

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“…Microglia is an immune regulatory cell of the nervous system, which initiates an immune response and induce neuroinflammation in the AD brains through toll-like receptors (TLR2, TLR4, TLR6, and TLR9) (Heneka et al, 2015b;Heneka et al, 2015a;Lee et al, 2009). However, ATSCs-conditioned medium can reduce the excessive activation of microglia and reduce the secretion of proinflammatory factors IL-1β and TNF-α by reducing the activation of TLR2 and TLR4 receptors in microglia (Mehrabadi et al, 2020). Lee et al (2010b) implanted MSCs into the brains of APP/PS1 transgenic mice and found that the phenotype of microglia in the cerebral cortex and hippocampus of mice changed to M2 type (Lee et al, 2010b).…”

Section: Mscs Reduce Aβ and Neuroinflammation Via Microglia Activationmentioning

confidence: 99%

“…Since then, it has been suggested that in neuron replacement therapy, there are still several obstacles to be resolved, such as the transplantation pathway, tumorigenesis and mutation, and the efficiency of neuronal differentiation (Prockop et al, 2003;Caruso and Parolini, 2015). However, with the indepth study of stem cells, more and more evidence has supported that MSCs enter the blood-brain barrier (BBB) by paracrine with soluble factors to improve the brain microenvironment (Ma et al, 2013;Lim et al, 2020;Chen et al, 2020a;Mehrabadi et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cells: As a multi-target cell therapy for clearing β-amyloid deposition in Alzheimer’s disease

Zhang¹,

Li²,

Du³

et al. 2022

Biocell

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Extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks of Alzheimer's disease (AD). Studies have shown that aggregates of extracellular Aβ can induce neuroinflammation mediated neurotoxic signaling through microglial activation and release of pro-inflammatory factors. Thus, modulation of Aβ might be a potential therapeutic strategy for modifying disease progression. Recently, a large number of reports have confirmed the beneficial effects of mesenchymal stem cells (MSCs) on AD. It is believed to reduce neuroinflammation, reduce Aβ amyloid deposits and NFTs, increase acetylcholine levels, promote neurogenesis, reduce neuronal damage, and improve working memory and cognition. In this review, we focus on the role of MSCs in clearing Aβ deposition. MSCs have the potential to modulate Aβ-related microenvironments via enhancement of autophagy, proteolysis of Aβ aggregates, phagocytic clearance of Aβ by microglial M2 polarization, decrease oxidative stress (OS), and correction of abnormal sphingolipid (SL) metabolism. With advantages in clinical applications, these data suggest that the use of MSCs as a multi-target modulator of Aβ would be an effective therapeutic approach in AD.

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Section: Mscs Reduce Aβ and Neuroinflammation Via Microglia Activationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells: As a multi-target cell therapy for clearing β-amyloid deposition in Alzheimer’s disease

Zhang¹,

Li²,

Du³

et al. 2022

Biocell

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“…Studies with the following characteristics were included in the study: (1) Studies investigating the effects of curcumin on Aβ plasma level in Alzheimer's disease or aged people with dementia, (2) Studies that reported mean ± SD for Aβ, or any other effect sizes from which the calculation of mean ± SD was possible, (3) Only studies that had placebo and intervention groups were selected and the only difference between the two groups was curcumin regime.…”

Section: Inclusion Criteriamentioning

confidence: 99%

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mentioning

confidence: 99%

Effect of Curcumin on Beta-Amyloid Plasma Level in Alzheimer Disease: A Systematic Review and Meta-analysis

Mehrabadi

Alinaghpour

Zahedi

2021

Int Clin Neurosci J

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IntroductionAlzheimer's disease is a common neurodegenerative disease worldwide. 1,2 The most important cause mentioned was the accumulation of beta-amyloid (Aβ) fibril in the central nervous system (CNS). 3 Actually disruption in Aβ homeostasis can lead to the accumulation of Aβ fibrils as plaques in the brain. 4,5 These plaques can be detected by microglia receptors and finally activate signal cascades into microglia that lead to the release of inflammatory factors from microglia. 6,7 So, in brain of patients with Alzheimer's disease, there is a widespread neuroinflammation that can lead to neuronal apoptosis and brain atrophy. 8 The deposition of Aβ protein is a prominent pathological hallmark of brains affected by Alzheimer's disease. For this reason, the inhibition of Aβ production, prevention of Aβ fibril formation and accumulation, destabilization of pre-formed Aβ are considered as attractive therapeutic methods for the treatment of Alzheimer's disease. 9,10 Many animal and clinical studies showed that curcumin as the main constituent of turmeric spice is an effective ingredient in reducing Aβ plaques in the brain models of Alzheimer's disease. 11,12 Curcumin is well-known as an anti-inflammation and anti-oxidant ingredient. 13 It is a lipophilic compound that can easily cross the blood-brain barrier and affect Aβ plaque. 13,14 It can destabilize the Aβ fibrils and prevent the accumulation of Aβ polymer. 15,16 Many animal studies indicated that curcumin could alter Aβ metabolism in Alzheimer animal models and improve cognition and spatial memory. [17][18][19] But in clinical studies there is controversial results about its effects on Aβ clearance and metabolism. 20,21 For this purpose, we aimed to review the studies which have been done in this area on the effects of curcumin on Aβ 1-40 plasma level in clinical studies to find how curcumin affects Aβ metabolism. Methods Search StrategyWe performed a systematic review and meta-analysis on three randomized clinical trial (RCTs) and one pilot study that assessed the effect of curcumin on Aβ plasma level in Alzheimer's disease. For this purpose, we searched PubMed and Scopus databases up to December 2020, using the following search terms: (curcumin OR diferuloylmethane OR curcuminoids OR turmeric OR "Indian saffron") AND ("Alzheimer disease" OR "Alzheimer's disease" OR "Alzheimer Syndrome" OR "Senile Dementia") AND (amyloid OR "Beta amyloid" OR Aβ) AND (Intervention OR "controlled trial" OR randomized OR random OR randomly OR placebo OR "clinical trial" OR trial OR "randomized controlled trial"

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“…Non-steroidal anti-in ammatory drugs (NSAIDs), the most important drugs for AD treatment widely, exhibits neuroprotection and antioxidation, suppress the production of free radical and the activation of nuclear factor-κB (NF-κB) and interleukins in the CNS [8,9]. However, NSAIDs can only delay neuroin ammatory progression of AD patients, failed to prevent neurodegeneration [10]. Hence, new ways for stopping neuroin ammation are needed to be discovered.…”

Section: Introductionmentioning

confidence: 99%

Forsythoside B attenuates memory impairment and neuroinflammation via inhibition on NF-κB signaling in Alzheimer’s disease

Kong

Jiang

Wang

et al. 2020

Preprint

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BackgroundAlzheimer’s disease (AD) is a type of progressive neurodegenerative disease related to neuroinflammation. Forsythoside B (FTS•B), a phenylethanoid glycoside isolated from plants, has been reported to exert various pharmacological effects. However, the neuroprotection of FTS•B related to neuroinflammation has not been systemically reported.MethodsIn amyloid precursor protein/presenilin 1 (APP/PS1) mice, behavioral tests including Morris water maze, Y maze and open field experiment were used to examine the cognitive function. Immunohistochemistry were used to analyze amyloid-beta (Aβ) deposition, Tau protein phosphorylation, the levels of 4-hydroxynonenal (4-HNE), glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule 1 (Iba1). Remarkably changed proteins related to neuroinflammation were filtered via proteomics and verified via enzyme-linked immunosorbent assay (ELISA) and western blot. Besides, BV-2 cells and HT22 cells were used to confirm the anti-neuroinflammation of FTS·B.ResultsFTS·B counteracted cognitive decline, ameliorated Aβ deposition and Tau protein phosphorylation, attenuated microglia and astrocytes activation in the cortex and/or hippocampus. Furthermore, FTS·B affected vital signaling, particularly by decreasing the activation of JNK-interacting protein 3/C-Jun NH2-terminal kinase (JIP3/JNK) and suppressing WD-repeat and FYVE-domain-containing protein 1/toll-like receptor 3 (WDFY1/TLR3), further suppressing the activation of nuclear factor-κB (NF-κB) signaling. In BV-2 and HT22 cells, FTS·B prevented lipopolysaccharide (LPS)-induced neuroinflammation and reduced the microglia-mediated neurotoxicity.ConclusionsFTS·B counteracted cognitive decline by triggering neurogenesis via signaling associated with inflammation, suggesting the promising therapeutic effects of FTS·B on AD treatment.# The two authors contribute equally to the project

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Hypoxic-conditioned medium from adipose tissue mesenchymal stem cells improved neuroinflammation through alternation of toll like receptor (TLR) 2 and TLR4 expression in model of Alzheimer's disease rats

Cited by 33 publications

References 42 publications

Mesenchymal stem cells: As a multi-target cell therapy for clearing β-amyloid deposition in Alzheimer’s disease

Mesenchymal stem cells: As a multi-target cell therapy for clearing β-amyloid deposition in Alzheimer’s disease

Effect of Curcumin on Beta-Amyloid Plasma Level in Alzheimer Disease: A Systematic Review and Meta-analysis

Forsythoside B attenuates memory impairment and neuroinflammation via inhibition on NF-κB signaling in Alzheimer’s disease

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