Research Progress of Targeting Neuro-Immune Inflammation in the Treatment of Alzheimer's Disease

Chen, Huize; Deng, Chujun; Meng, Zeyu; Meng, Shumei

doi:10.31083/j.fbl2711312

Cited by 5 publications

(2 citation statements)

References 89 publications

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“…Microglia are a class of intrinsic immune cells found in the central nervous system and are involved in immune surveillance, signaling, injury response, phagocytosis of cellular debris and repair of synapses ( 33 , 34 ). Since microglia are a major source of inflammatory factors, their overactivation leads to neuroinflammation, which is key to the development of many neurological diseases ( 35 , 36 ). Activated microglia are generally divided into two phenotypes, M1 and M2, which exert proinflammatory and anti-inflammatory effects, respectively.…”

Section: Discussionmentioning

confidence: 99%

Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation

Xiong

Kang

et al. 2023

Front. Immunol.

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BackgroundNeuroinflammation is an important factor causing numerous neurodegenerative pathologies. Inflammation can lead to abnormal neuronal structure and function and even death, followed by cognitive dysfunction. There is growing evidence that chlorogenic acid has anti-inflammatory effects and immunomodulatory activity.PurposeThe aim of this study was to elucidate the potential targets and molecular mechanisms of chlorogenic acid in the treatment of neuroinflammation.MethodsWe used the lipopolysaccharide-induced neuroinflammation mouse model and the lipopolysaccharide-stimulated BV-2 cells in vitro model. Behavioral scores and experiments were used to assess cognitive dysfunction in mice. HE staining and immunohistochemistry were used to assess neuronal damage in the mouse brain. Immunofluorescence detected microglia polarization in mouse brain. Western blot and flow cytometry detected the polarization of BV-2 cells. The migration of BV-2 cells was detected by wound healing assay and transwell assay. Potential targets for chlorogenic acid to exert protective effects were predicted by network pharmacology. These targets were then validated using molecular docking and experiments.ResultsThe results of in vivo experiments showed that chlorogenic acid had an obvious ameliorating effect on neuroinflammation-induced cognitive dysfunction. We found that chlorogenic acid was able to inhibit BV-2 cells M1 polarization and promote BV-2 cells M2 polarization in vitro while also inhibiting the abnormal migration of BV-2 cells. Based on the network pharmacology results, we identified the TNF signaling pathway as a key signaling pathway in which chlorogenic acid exerts anti-neuroinflammatory effects. Among them, Akt1, TNF, MMP9, PTGS2, MAPK1, MAPK14, and RELA are the core targets for chlorogenic acid to function.ConclusionChlorogenic acid can inhibit microglial polarization toward the M1 phenotype and improve neuroinflammation-induced cognitive dysfunction in mice by modulating these key targets in the TNF signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation

Xiong

Kang

et al. 2023

Front. Immunol.

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“…Moreover, their role in Aβ clearance becomes compromised, further exacerbating the disease's progression. Recent findings also indicate that astrocytes may contribute to tau hyperphosphorylation, a critical event in NFT formation [20,21].…”

Section: Role Of Neuroinflammation In the Progression Of Alzheimer's ...mentioning

confidence: 97%

Untangling Tau: Molecular Insights into Neuroinflammation, Pathophysiology, and Emerging Immunotherapies

Davidson,

Krider,

Borsellino

et al. 2023

CIMB

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Neuroinflammation, a core pathological feature observed in several neurodegenerative diseases, including Alzheimer’s disease (AD), is rapidly gaining attention as a target in understanding the molecular underpinnings of these disorders. Glial cells, endothelial cells, peripheral immune cells, and astrocytes produce a variety of pro-inflammatory mediators that exacerbate the disease progression. Additionally, microglial cells play a complex role in AD, facilitating the clearance of pathological amyloid-beta peptide (Aβ) plaques and aggregates of the tau protein. Tau proteins, traditionally associated with microtubule stabilization, have come under intense scrutiny for their perturbed roles in neurodegenerative conditions. In this narrative review, we focus on recent advances from molecular insights that have revealed aberrant tau post-translational modifications, such as phosphorylation and acetylation, serving as pathological hallmarks. These modifications also trigger the activation of CNS-resident immune cells, such as microglia and astrocytes substantially contributing to neuroinflammation. This intricate relationship between tau pathologies and neuroinflammation fosters a cascading impact on neural pathophysiology. Furthermore, understanding the molecular mechanisms underpinning tau’s influence on neuroinflammation presents a frontier for the development of innovative immunotherapies. Neurodegenerative diseases have been relatively intractable to conventional pharmacology using small molecules. We further comprehensively document the many alternative approaches using immunotherapy targeting tau pathological epitopes and structures with a wide array of antibodies. Clinical trials are discussed using these therapeutic approaches, which have both promising and disappointing outcomes. Future directions for tau immunotherapies may include combining treatments with Aβ immunotherapy, which may result in more significant clinical outcomes for neurodegenerative diseases.

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Oolong tea polyphenols affect the inflammatory response to improve cognitive function by regulating gut microbiota

Song

Zhang

Hong

et al. 2023

Journal of Functional Foods

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Research Progress of Targeting Neuro-Immune Inflammation in the Treatment of Alzheimer's Disease

Cited by 5 publications

References 89 publications

Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation

Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation

Untangling Tau: Molecular Insights into Neuroinflammation, Pathophysiology, and Emerging Immunotherapies

Oolong tea polyphenols affect the inflammatory response to improve cognitive function by regulating gut microbiota

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