Shedding Light on NF-κB Functions in Cellular Organelles

Carrà, Giovanna; Avalle, Lidia; Seclì, Laura; Brancaccio, Mara; Morotti, Alessandro

doi:10.3389/fcell.2022.841646

Cited by 11 publications

(6 citation statements)

References 89 publications

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“…Subsequently, this mature NF-κB2 p52 relocates into the nucleus in conjunction with ReIB. A crucial player in orchestrating this degradation process is a signaling molecule called NF-κB-inducing kinase (NIK) ( 66 , 67 ). NIK effectively instigates the activation of IKKα and works in collaboration with it to facilitate the phosphorylation of p100 ( 34 , 68 ).…”

Section: Nuclear Factor Kappa B (Nf-κb): a Pioneer Shaping The Landsc...mentioning

confidence: 99%

Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Fornari Laurindo,

Aparecido Dias,

Cressoni Araújo

et al. 2024

Front. Immunol.

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The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as a significant contributing factor. It involves the activation of microglia and astrocytes, leading to the release of pro-inflammatory cytokines and chemokines and the infiltration of peripheral leukocytes into the central nervous system (CNS). These instances result in neuronal damage and neurodegeneration through activated nucleotide-binding domain and leucine-rich repeat containing (NLR) family pyrin domain containing protein 3 (NLRP3) and nuclear factor kappa B (NF-kB) pathways and decreased nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Due to limited effectiveness regarding the inhibition of neuroinflammatory targets using conventional drugs, there is challenging growth in the search for innovative therapies for alleviating neuroinflammation in CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling and Expression, Cold Exposure, and Fibrin-Targeted strategies significantly promise to mitigate neuroinflammatory processes. These approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such as Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson’s Disease, and Alzheimer’s Disease. While the findings are promising, immunomodulatory therapies often face limitations due to Immune-Related Adverse Events. Therefore, the conduction of randomized clinical trials in this matter is mandatory, and will pave the way for a promising future in the development of new medicines with specific therapeutic targets.

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Section: Nuclear Factor Kappa B (Nf-κb): a Pioneer Shaping The Landsc...mentioning

confidence: 99%

Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Fornari Laurindo,

Aparecido Dias,

Cressoni Araújo

et al. 2024

Front. Immunol.

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“…NF-κB has a dual role in the regulation of apoptosis, which is dependent on the balance between genes that controls cell survival and apoptosis. 257 In cancer cells, NF-κB activity interacts with various apoptotic and survival proteins. NF-κB can regulate PTEN through transcriptionally activate Snail, a repressor of PTEN, and thus regulate cell survival.…”

Section: Nf-κb Signaling In Human Diseasesmentioning

confidence: 99%

NF-κB in biology and targeted therapy: new insights and translational implications

Guo,

Jin,

Chen

et al. 2024

Sig Transduct Target Ther

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NF-κB signaling has been discovered for nearly 40 years. Initially, NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have discovered that its role can be expanded to a variety of signaling mechanisms, biological processes, human diseases, and treatment options. In this review, we first scrutinize the research process of NF-κB signaling, and summarize the composition, activation, and regulatory mechanism of NF-κB signaling. We investigate the interaction of NF-κB signaling with other important pathways, including PI3K/AKT, MAPK, JAK-STAT, TGF-β, Wnt, Notch, Hedgehog, and TLR signaling. The physiological and pathological states of NF-κB signaling, as well as its intricate involvement in inflammation, immune regulation, and tumor microenvironment, are also explicated. Additionally, we illustrate how NF-κB signaling is involved in a variety of human diseases, including cancers, inflammatory and autoimmune diseases, cardiovascular diseases, metabolic diseases, neurological diseases, and COVID-19. Further, we discuss the therapeutic approaches targeting NF-κB signaling, including IKK inhibitors, monoclonal antibodies, proteasome inhibitors, nuclear translocation inhibitors, DNA binding inhibitors, TKIs, non-coding RNAs, immunotherapy, and CAR-T. Finally, we provide an outlook for research in the field of NF-κB signaling. We hope to present a stereoscopic, comprehensive NF-κB signaling that will inform future research and clinical practice.

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“…Certain extracellular mediators and cytokines may mediate the synergistic crosstalk between nuclear and mitochondrial gene expression. 55 Research has shown that the import of Signal transducer and activator of transcription 3 (STAT3) into mitochondria requires partner coordination and posttranslational modifications of STAT3, such as Ser727 phosphorylation and K87 acetylation. 56 Similarly, the RelA/IκBα complex also requires partner coordination to enter mitochondria.…”

Section: Rela and Stat3mentioning

confidence: 99%

“…NF‐κB participates in the regulation of classical nuclear genes and also plays a role in mitochondrial gene expression. Certain extracellular mediators and cytokines may mediate the synergistic cross‐talk between nuclear and mitochondrial gene expression 55 . Research has shown that the import of Signal transducer and activator of transcription 3 (STAT3) into mitochondria requires partner coordination and posttranslational modifications of STAT3, such as Ser727 phosphorylation and K87 acetylation 56 .…”

Section: Biological Role Of Nf‐κb Family In Mitochondriamentioning

confidence: 99%

Biological role of mitochondrial TLR4‐mediated NF‐κB signaling pathway in central nervous system injury

Wu,

Song,

Wang

et al. 2024

Cell Biochemistry & Function

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Previous studies suggested that central nervous system injury is often accompanied by the activation of Toll‐like receptor 4/NF‐κB pathway, which leads to the upregulation of proapoptotic gene expression, causes mitochondrial oxidative stress, and further aggravates the inflammatory response to induce cell apoptosis. Subsequent studies have shown that NF‐κB and IκBα can directly act on mitochondria. Therefore, elucidation of the specific mechanisms of NF‐κB and IκBα in mitochondria may help to discover new therapeutic targets for central nervous system injury. Recent studies have suggested that NF‐κB (especially RelA) in mitochondria can inhibit mitochondrial respiration or DNA expression, leading to mitochondrial dysfunction. IκBα silencing will cause reactive oxygen species storm and initiate the mitochondrial apoptosis pathway. Other research results suggest that RelA can regulate mitochondrial respiration and energy metabolism balance by interacting with p53 and STAT3, thus initiating the mitochondrial protection mechanism. IκBα can also inhibit apoptosis in mitochondria by interacting with VDAC1 and other molecules. Regulating the biological role of NF‐κB signaling pathway in mitochondria by targeting key proteins such as p53, STAT3, and VDAC1 may help maintain the balance of mitochondrial respiration and energy metabolism, thereby protecting nerve cells and reducing inflammatory storms and death caused by ischemia and hypoxia.

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Shedding Light on NF-κB Functions in Cellular Organelles

Cited by 11 publications

References 89 publications

Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

NF-κB in biology and targeted therapy: new insights and translational implications

Biological role of mitochondrial TLR4‐mediated NF‐κB signaling pathway in central nervous system injury

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