Triggering Receptor Expressed on Myeloid Cells 2 Protects Dopaminergic Neurons by Promoting Autophagy in the Inflammatory Pathogenesis of Parkinson’s Disease

Huang, Wei; Lv, Qiankun; Yan, Xiao; Zhong, Zhisheng; Hu, Binbin; Yan, Si; Yan, Yishu; Shi, Tongguo; Jiang, Lijuan; Li, Wen; Lu, Guohui

doi:10.3389/fnins.2021.745815

Cited by 11 publications

(10 citation statements)

References 55 publications

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“…The ratio of LC3‐II/I was more when TREM2 was highly expressed compared to the control group both in vivo and in vitro. This finding suggests that at inflammatory conditions TREM2 boosts autophagy in microglia (Huang et al, 2021).…”

Section: Effects Of Trem2 On Brain Metabolism and Autophagymentioning

confidence: 89%

“…These findings imply that TREM2 keeps microglia in high metabolic states by enhancing mTOR pathway activity, allowing microglia to gather around amyloid plaques in AD models. Studies conducted both in vivo and in vitro suggested that overexpressing TREM2 could inhibit the p38 MAPK pathway as well as the mTOR pathway (Huang et al, 2021). This results in the inhibition of microglial activation and the reduction of damage via inhibiting autophagy in the microglia, demonstrating the anti‐inflammatory and neuroprotective effects of TREM2.…”

Section: Effects Of Trem2 On Brain Metabolism and Autophagymentioning

confidence: 99%

“…This results in the inhibition of microglial activation and the reduction of damage via inhibiting autophagy in the microglia, demonstrating the anti‐inflammatory and neuroprotective effects of TREM2. Indeed, TREM2 overexpression reduced neuronal apoptosis and improved motor functions after the microglial activation (Huang et al, 2021). Thus, by modulation of the key regulators of cerebral metabolism, autophagy and inflammatory pathways, TREM2 appears to be an important link between pathological changes associated with the disease and neuroinflammation.…”

Section: Effects Of Trem2 On Brain Metabolism and Autophagymentioning

confidence: 99%

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TREM2 signalling as a multifaceted player in brain homoeostasis and a potential target for Alzheimer's disease treatment

Ayyubova

2023

Eur J of Neuroscience

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Triggering receptor expressed on myeloid cells-2 (TREM2) has crucial roles in microglial physiology, differentiation, metabolism and survival. Genome-wide association studies (GWAS) show that genetic mutations of the TREM2 increase the risk of late-onset Alzheimer's disease (AD) by two to four times, disrupting the microglial function in reducing the progression of the disease.Accumulating data show that TREM2 function in AD is related primarily to the clearance of soluble and insoluble amyloid beta (Aβ42) aggregates from the brain. TREM2 also ameliorates the pathological effects of activated microglia on neuronal tau pathology, demonstrating its protective anti-inflammatory effects. However, since the excessive activation of TREM2 signalling can inhibit pro-inflammatory reactions and suppress the role of microglia in immune surveillance, at the late stages of the disease, it might promote immune tolerance, which is detrimental. The contradictory effects of TREM2 mutations on brain amyloidopathy and tauopathy in multiple mouse models, as well as studies revealing various effects of TREM2 overexpression, complicate the understanding of the role that TREM2 plays in AD aetiopathogenesis. In this review, we summarize the latest developments regarding the significance of TREM2 signalling in the stability of microglial pro-and antiinflammatory activations and propose the mechanisms that should be targeted in the future to treat AD.

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Section: Effects Of Trem2 On Brain Metabolism and Autophagymentioning

confidence: 89%

Section: Effects Of Trem2 On Brain Metabolism and Autophagymentioning

confidence: 99%

Section: Effects Of Trem2 On Brain Metabolism and Autophagymentioning

confidence: 99%

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TREM2 signalling as a multifaceted player in brain homoeostasis and a potential target for Alzheimer's disease treatment

Ayyubova

2023

Eur J of Neuroscience

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“…During the experiment, the body weight of the mice in each group was monitored weekly. The pole climbing test, the hanging test, and the rotarod test were used to assess motor coordination and balance in mice …”

Section: Methodsmentioning

confidence: 99%

Biomimetic Biomembrane Encapsulation and Targeted Delivery of a Nitric Oxide Release Platform for Therapy of Parkinson’s Disease

Huang

Xiang

et al. 2023

ACS Biomater. Sci. Eng.

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The existence of the blood−brain barrier (BBB) and the complex inflammatory environment in the brain are two major obstacles in the treatment of Parkinson's disease (PD). As a target group, we modified the red blood cell membrane (RBCM) on the surface of upconversion nanoparticles (UCNPs) in this study to effectively target the brain. Mesoporous silicon, coated with UCNPs (UCM), was loaded with S-nitrosoglutathione (GSNO) as the nitric oxide (NO) donor. Then, UCNPs were excited to emit green light (540 nm) by 980 nm near-infrared (NIR). In addition, it produced a lightresponsive anti-inflammatory effect by promoting the release of NO from GSNO and lowering the brain's level of proinflammatory factors. A series of experiments demonstrated that this strategy could effectively mitigate the inflammatory response damage of neurons in the brain.

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“…Important role of MAPK signaling in Aβ generation (Du et al, 2019) and cognitive decline independent of amyloid pathology has been proposed in AD (Johnson et al, 2022). Multiple levels of evidence support the TREM2-induced MAPK signaling in PD pathogenesis (Huang et al, 2021;Ruganzu et al, 2022). Microglial MAPK over-activity has been extensively studied in MS (Ten Bosch et al, 2021), while the therapeutic potential of MAPK pathway inhibition in demyelination recovery has also been proposed (Suo et al, 2019).…”

Section: Neuroinflammation Promoting Signaling Pathwaysmentioning

confidence: 99%

Shared miRNA landscapes of COVID-19 and neurodegeneration confirm neuroinflammation as an important overlapping feature

Trampuž

Vogrinc

Goričar

et al. 2023

Front. Mol. Neurosci.

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IntroductionDevelopment and worsening of most common neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, have been associated with COVID-19 However, the mechanisms associated with neurological symptoms in COVID-19 patients and neurodegenerative sequelae are not clear. The interplay between gene expression and metabolite production in CNS is driven by miRNAs. These small non-coding molecules are dysregulated in most common neurodegenerative diseases and COVID-19.MethodsWe have performed a thorough literature screening and database mining to search for shared miRNA landscapes of SARS-CoV-2 infection and neurodegeneration. Differentially expressed miRNAs in COVID-19 patients were searched using PubMed, while differentially expressed miRNAs in patients with five most common neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and multiple sclerosis) were searched using the Human microRNA Disease Database. Target genes of the overlapping miRNAs, identified with the miRTarBase, were used for the pathway enrichment analysis performed with Kyoto Encyclopedia of Genes and Genomes and Reactome.ResultsIn total, 98 common miRNAs were found. Additionally, two of them (hsa-miR-34a and hsa-miR-132) were highlighted as promising biomarkers of neurodegeneration, as they are dysregulated in all five most common neurodegenerative diseases and COVID-19. Additionally, hsa-miR-155 was upregulated in four COVID-19 studies and found to be dysregulated in neurodegeneration processes as well. Screening for miRNA targets identified 746 unique genes with strong evidence for interaction. Target enrichment analysis highlighted most significant KEGG and Reactome pathways being involved in signaling, cancer, transcription and infection. However, the more specific identified pathways confirmed neuroinflammation as being the most important shared feature.DiscussionOur pathway based approach has identified overlapping miRNAs in COVID-19 and neurodegenerative diseases that may have a valuable potential for neurodegeneration prediction in COVID-19 patients. Additionally, identified miRNAs can be further explored as potential drug targets or agents to modify signaling in shared pathways.Graphical AbstractShared miRNA molecules among the five investigated neurodegenerative diseases and COVID-19 were identified. The two overlapping miRNAs, hsa-miR-34a and has-miR-132, present potential biomarkers of neurodegenerative sequelae after COVID-19. Furthermore, 98 common miRNAs between all five neurodegenerative diseases together and COVID-19 were identified. A KEGG and Reactome pathway enrichment analyses was performed on the list of shared miRNA target genes and finally top 20 pathways were evaluated for their potential for identification of new drug targets. A common feature of identified overlapping miRNAs and pathways is neuroinflammation. AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; COVID-19, coronavirus disease 2019; HD, Huntington’s disease; KEGG, Kyoto Encyclopedia of Genes and Genomes; MS, multiple sclerosis; PD, Parkinson’s disease.

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Triggering Receptor Expressed on Myeloid Cells 2 Protects Dopaminergic Neurons by Promoting Autophagy in the Inflammatory Pathogenesis of Parkinson’s Disease

Cited by 11 publications

References 55 publications

TREM2 signalling as a multifaceted player in brain homoeostasis and a potential target for Alzheimer's disease treatment

TREM2 signalling as a multifaceted player in brain homoeostasis and a potential target for Alzheimer's disease treatment

Biomimetic Biomembrane Encapsulation and Targeted Delivery of a Nitric Oxide Release Platform for Therapy of Parkinson’s Disease

Shared miRNA landscapes of COVID-19 and neurodegeneration confirm neuroinflammation as an important overlapping feature

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