LRP1 knockdown aggravates Aβ1–42-stimulated microglial and astrocytic neuroinflammatory responses by modulating TLR4/NF-κB/MAPKs signaling pathways

He, Yingying; Ruganzu, John Bosco; Jin, Hui; Peng, Xiaoqian; Ji, Shengfeng; Ma, Yongkui; Zheng, Liming; Yang, Weina

doi:10.1016/j.yexcr.2020.112166

Cited by 26 publications

(23 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After binding to Aβ, TLR4 recruits the pivotal downstream signaling adaptor molecules MyD88 and TRAF6, activating multiple downstream signaling molecules, including the MAPK family. It is well established that MAPK signaling pathway activation is critical for the production of various proin ammatory cytokines and mediators [6,42]. To demonstrate that downregulation of TREM2 expression can aggravate neuroin ammation via TLR4-mediated MAPK signaling pathway.…”

Section: Downregulation Of Trem2 Expression Enhanced Neuroin Ammatorymentioning

confidence: 95%

“…6-month-old male APP/PS1 mice and their age and sex-matched WT mice were randomized into the WT group (n = 10), APP/PS1 group (n = 10), APP/PS1 + LV-Con group (n = 10), and APP/PS1 + LV-shTREM2 group (n = 10). Intracerebral injection of lentiviral particles was performed as previously described [6,24]. Brie y, mice were anesthetized by intraperitoneal injection of sodium pentobarbital and placed on a stereotaxic apparatus (Shenzhen RWD Life Science Co., Ltd. China).…”

Section: Intracerebral Injection Of Lentiviral Particlesmentioning

confidence: 99%

“…The toxic oligomers of Aβ 1−42 were prepared as previously described [6,35]. Brie y, lyophilized Aβ 1−42 peptide was dissolved in HFIP at a concentration of 1 mg/mL, separated into aliquots in sterile microcentrifuge tubes, dried under vacuum, and stored at − 80°C.…”

Section: Preparation Of Aβ 1−42 Oligomersmentioning

confidence: 99%

“…Cell transfection was conducted as previously described [6,24]. Brie y, 1 × 10 4 BV2 cells were seeded on 6-well plates and incubated in a growth medium until 20-30% con uence.…”

Section: Cell Transfection and Drug Treatmentmentioning

confidence: 99%

“…Microglia activation was found to be related to the interaction between Aβ with several receptors including toll-like receptor 4 (TLR4) in AD patients and animal models [5]. Aβ binding to TLR4 activates the mitogen-activated protein kinase (MAPK) signaling pathway by its downstream molecule myeloid differential protein 88 (MyD88) and TNF-receptor-associated factor 6 (TRAF6) [6,7]. When activated, microglia aggregate around Aβ plaques and produce various proin ammatory cytokines and in ammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), reactive oxygen species, and nitric oxide [3,8].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Downregulation of TREM2 Expression Exacerbates Neuroinflammatory Responses Through TLR4-Mediated MAPK Signaling Pathway in a Transgenic Mouse Model of Alzheimer’s Disease

Ruganzu¹,

Peng²,

He³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Activation of glial cells and neuroinflammation play an important role in the onset and development of Alzheimer’s disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-specific receptor in the brain that is involved in regulating neuroinflammation. However, the precise effects of TREM2 on neuroinflammatory responses and its underlying molecular mechanisms in AD have not been studied in detail. Here, we employed a lentiviral-mediated strategy to downregulation of TREM2 expression on microglia in the brain of APPswe/PS1dE9 (APP/PS1) transgenic mice and BV2 cells. Our results showed that TREM2 downregulation significantly aggravated AD-related neuropathology including Aβ accumulation, peri-plaque microgliosis and astrocytosis, as well as neuronal and synapse-associated proteins loss, which was accompanied by a decline in cognitive ability. The further mechanistic study revealed that downregulation of TREM2 expression initiated neuroinflammatory responses through toll-like receptor 4 (TLR4)-mediated mitogen-activated protein kinase (MAPK) signaling pathway and subsequent stimulating the production of pro-inflammatory cytokines in vivo and in vitro. Moreover, blockade of p38, JNK, and ERK1/2 inhibited the release of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) induced by Aβ1−42 in TREM2-knocked down BV2 cells. Taken together, these findings indicated that TREM2 might be a potential therapeutic target for AD and other neuroinflammation related diseases.

show abstract

Section: Downregulation Of Trem2 Expression Enhanced Neuroin Ammatorymentioning

confidence: 95%

Section: Intracerebral Injection Of Lentiviral Particlesmentioning

confidence: 99%

Section: Preparation Of Aβ 1−42 Oligomersmentioning

confidence: 99%

“…Cell transfection was conducted as previously described [6,24]. Brie y, 1 × 10 4 BV2 cells were seeded on 6-well plates and incubated in a growth medium until 20-30% con uence.…”

Section: Cell Transfection and Drug Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Downregulation of TREM2 Expression Exacerbates Neuroinflammatory Responses Through TLR4-Mediated MAPK Signaling Pathway in a Transgenic Mouse Model of Alzheimer’s Disease

Ruganzu¹,

Peng²,

He³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Regulation of beta‐amyloid for the treatment of Alzheimer's disease: Research progress of therapeutic strategies and bioactive compounds

Qiu

Liu

et al. 2023

Medicinal Research Reviews

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is difficult to treat. Extracellular amyloid is the principal pathological criterion for the diagnosis of AD. Amyloid β (Aβ) interacts with various receptor molecules on the plasma membrane and mediates a series of signaling pathways that play a vital role in the occurrence and development of AD. Research on receptors that interact with Aβ is currently ongoing. Overall, there are no effective medications to treat AD. In this review, we first discuss the importance of Aβ in the pathogenesis of AD, then summarize the latest progress of Aβ‐related targets and compounds. Finally, we put forward the challenges and opportunities in the development of effective AD therapies.

show abstract

Ginsenoside compound K acts via LRP1 to alleviate Amyloid β42-induced neuroinflammation in microglia by suppressing NF-κB

Jiao

Jia

2022

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

LRP1 knockdown aggravates Aβ1–42-stimulated microglial and astrocytic neuroinflammatory responses by modulating TLR4/NF-κB/MAPKs signaling pathways

Cited by 26 publications

References 41 publications

Downregulation of TREM2 Expression Exacerbates Neuroinflammatory Responses Through TLR4-Mediated MAPK Signaling Pathway in a Transgenic Mouse Model of Alzheimer’s Disease

Downregulation of TREM2 Expression Exacerbates Neuroinflammatory Responses Through TLR4-Mediated MAPK Signaling Pathway in a Transgenic Mouse Model of Alzheimer’s Disease

Regulation of beta‐amyloid for the treatment of Alzheimer's disease: Research progress of therapeutic strategies and bioactive compounds

Ginsenoside compound K acts via LRP1 to alleviate Amyloid β42-induced neuroinflammation in microglia by suppressing NF-κB

Contact Info

Product

Resources

About