Beta-Amyloid Increases the Expression Levels of Tid1 Responsible for Neuronal Cell Death and Amyloid Beta Production

Zhou, Chunyu; Taslima, Ferdous; Abdelhamid, Mona; Kim, Sung Woo; Akatsu, Hiroyasu; Michikawa, Makoto; Jung, Cha-Gyun

doi:10.1007/s12035-019-01807-2

Cited by 15 publications

(11 citation statements)

References 62 publications

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“…Another key mediator of neuroinflammation is JNK in the central nervous system. Patients with AD show upregulated expression of JNK in the brains, which promotes amyloidogenic APP cleavage and amyloid plaque formation [55]. Activated astrocytes and microglia increases the expression of GFAP and Iba1, respectively [33], and we showed FTS•B reduced the expression of GFAP and Iba1 in the hippocampus, indicating that FTS•B suppressed the activation of astrocytes and microglia in AD mice.…”

Section: Discussionmentioning

confidence: 59%

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

Kong

Jiang

Wang

et al. 2020

J Neuroinflammation

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Background Neuroinflammation is a principal element in Alzheimer’s disease (AD) pathogenesis, so anti-inflammation may be a promising therapeutic strategy. Forsythoside B (FTS•B), a phenylethanoid glycoside isolated from Forsythiae fructus, has been reported to exert anti-inflammatory effects. However, no studies have reported whether the anti-inflammatory properties of FTS•B have a neuroprotective effect in AD. In the present study, these effects of FTS•B were investigated using amyloid precursor protein/presenilin 1 (APP/PS1) mice, BV-2 cells, and HT22 cells. Methods APP/PS1 mice were administered FTS•B intragastrically for 36 days. Behavioral tests were then carried out to examine cognitive functions, including the Morris water maze, Y maze, and open field experiment. Immunohistochemistry was used to analyze the deposition of amyloid-beta (Aβ), the phosphorylation of tau protein, and the levels of 4-hydroxynonenal, glial fibrillary acidic protein, and ionized calcium-binding adapter molecule 1 in the hippocampus. Proteins that showed marked changes in levels related to neuroinflammation were identified using proteomics and verified using enzyme-linked immunosorbent assay and western blot. BV-2 and HT22 cells were also used to confirm the anti-neuroinflammatory effects of FTS•B. Results In APP/PS1 mice, FTS•B counteracted cognitive decline, ameliorated the deposition of Aβ and the phosphorylation of tau protein, and attenuated the activation of microglia and astrocytes in the cortex and hippocampus. FTS•B affected vital signaling, particularly by decreasing the activation of JNK-interacting protein 3/C-Jun NH2-terminal kinase 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-induced neuroinflammation and reduced the microglia-mediated neurotoxicity. Conclusions FTS•B effectively counteracted cognitive decline by regulating neuroinflammation via NF-κB signaling in APP/PS1 mice, providing preliminary experimental evidence that FTS•B is a promising therapeutic agent in AD treatment.

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Section: Discussionmentioning

confidence: 59%

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

Kong

Jiang

Wang

et al. 2020

J Neuroinflammation

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“…Although we did not obtain direct evidence of the induction of oxidative stress in the brain of Tg2576 mice housed at 30 °C, we found that the sustained high body temperature increased the total levels of stress-activated protein kinases, such as JNK, p38, and ERK kinases, and consequently led to the enhancement of their phosphorylation. Several studies have demonstrated that the activation of JNK may be linked to the induction of BACE1 32 , 33 . The activation of JNK is known to be an important factor in the pathogenesis of AD, which contributes to the enhancement of Aβ generation 32 and tau phosphorylation 34 .…”

Section: Discussionmentioning

confidence: 99%

Sustained high body temperature exacerbates cognitive function and Alzheimer’s disease-related pathologies

Jung

Kato

Zhou

et al. 2022

Sci Rep

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Global warming is a serious public health threat to people worldwide. High body temperature is one of the important risk factors for Alzheimer’s disease (AD), and the body temperature of AD patients has been found to be significantly higher than that of elderly control subjects. However, the effects of high body temperature on cognitive function and AD pathologies have not been completely elucidated. We report here that Tg2576 mice housed at a high ambient temperature of 30 °C for 13 months showed an increase in the body temperature, which is accompanied by memory impairment and an enhancement of amyloid-β peptides (Aβ) generation through the upregulation of β-site APP cleaving enzyme 1 (BACE1) level and decrease in the level of an Aβ-degrading enzyme, neprilysin (NEP) in the brain, compared with those of Tg2576 mice at 23 °C. High body temperature also increased the levels of heat shock proteins (HSPs), stress-stimulated kinases such as JNK, and total tau, leading to the enhancement of tau phosphorylation at 30 °C. Taken together, our findings suggest that high body temperature exacerbates cognitive function and AD pathologies, which provides a mechanistic insight for its prevention.

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“…The DnaJ homolog subfamily A member 3 (Dnaja3) regulates apoptotic signal transduction by influencing cytochrome C release from the mitochondria and activating caspase 3 [ 47 ]. Dnaja3 protein was upregulated in the hippocampi of Alzheimer’s disease (AD) patients and the AD mouse model, and Dnaja3 induced amyloid β42 (Aβ42) production and neuronal apoptosis, which played a crucial role in the pathogenesis of AD [ 48 , 49 ]. Recently, a growing body of evidence has indicated that the LCN2 was associated with AD pathogenesis, vascular dementia, and other neurodegenerative dementias [ 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

The effect of lipocalin-2 (LCN2) on apoptosis: a proteomics analysis study in an LCN2 deficient mouse model

Han

Wang

2021

BMC Genomics

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Background Recent studies have shown that lipocalin-2 (LCN2) has multiple functions involved in various biological and pathological processes including energy homeostasis, cancer, inflammation, and apoptosis. We aimed to investigate the effect of LCN2 on apoptosis that influences the pathogenetic process of metabolic diseases and cancer. Methods We performed a proteomics analysis of livers taken from LCN2-knockout mice and wild type mice by using label-free LC-MS/MS quantitative proteomics. Results Proteomic analysis revealed that there were 132 significantly differentially expressed proteins (49 upregulated and 83 downregulated) among 2140 proteins in the liver of LCN2-knockout mice compared with wild type mice. Of these, seven apoptosis-associated proteins were significantly upregulated and seven apoptosis-associated proteins downregulated. Conclusion Proteomics demonstrated that there were seven upregulated and seven downregulated apoptosis-associated proteins in liver of LCN2-knockout mice. It is important to clarify the effect of LCN2 on apoptosis that might contribute to the pathogenesis of insulin resistance, cancer, and various nervous system diseases.

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Beta-Amyloid Increases the Expression Levels of Tid1 Responsible for Neuronal Cell Death and Amyloid Beta Production

Cited by 15 publications

References 62 publications

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

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

Sustained high body temperature exacerbates cognitive function and Alzheimer’s disease-related pathologies

The effect of lipocalin-2 (LCN2) on apoptosis: a proteomics analysis study in an LCN2 deficient mouse model

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