ArticleCell death & disease2014
TLR4 mediates the impairment of ubiquitin-proteasome and autophagy-lysosome pathways induced by ethanol treatment in brain.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 73 citations in OpenAlex.
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- The ubiquitin-proteasome system and learning-dependent synaptic plasticity - A 10 year update.Neuroscience and biobehavioral reviews · 2023Review
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- Chronic Ethanol Causes Persistent Increases in Alzheimer's Tau Pathology in Female 3xTg-AD Mice: A Potential Role for Lysosomal Impairment.Frontiers in behavioral neuroscience · 2022Article
- Mechanisms of Ethanol-Induced Cerebellar Ataxia: Underpinnings of Neuronal Death in the Cerebellum.International journal of environmental research and public health · 2021Review
- Immunoproteasome impairment via β5i/LMP7-deletion leads to sustained pancreatic injury from experimental pancreatitis.Journal of cellular and molecular medicine · 2021Article
- Aversive Learning Deficits and Depressive-Like Behaviors Are Accompanied by an Increase in Oxidative Stress in a Rat Model of Fetal Alcohol Spectrum Disorders: The Protective Effect of Rapamycin.International journal of molecular sciences · 2021Article
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- Cell Clearing Systems as Targets of Polyphenols in Viral Infections: Potential Implications for COVID-19 Pathogenesis.Antioxidants (Basel, Switzerland) · 2020Review
- Merging the Multi-Target Effects of Phytochemicals in Neurodegeneration: From Oxidative Stress to Protein Aggregation and Inflammation.Antioxidants (Basel, Switzerland) · 2020Review
- A Re-Appraisal of Pathogenic Mechanisms Bridging Wet and Dry Age-Related Macular Degeneration Leads to Reconsider a Role for Phytochemicals.International journal of molecular sciences · 2020Review
- Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies.International journal of molecular sciences · 2020Review
- Neural Stem Cells from Shank3-ko Mouse Model Autism Spectrum Disorders.Molecular neurobiology · 2020Article
- Hydrogen: A Novel Option in Human Disease Treatment.Oxidative medicine and cellular longevity · 2020Review
- Lack of TLR4 modifies the miRNAs profile and attenuates inflammatory signaling pathways.PloS one · 2020Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
New evidence indicates the involvement of protein degradation dysfunctions in neurodegeneration, innate immunity response and alcohol hepatotoxicity. We recently demonstrated that ethanol increases brain proinflammatory mediators and causes brain damage by activating Toll-like receptor 4 (TLR4) signaling in glia. However, it is uncertain if the ubiquitin-proteasome and autophagy-lysosome pathways are involved in ethanol-induced brain damage and whether the TLR4 response is implicated in proteolytic processes. Using the cerebral cortex of WT and TLR4-knockout mice with and without chronic ethanol treatment, we demonstrate that ethanol induces poly-ubiquitinated proteins accumulation and promotes immunoproteasome activation by inducing the expression of β2i, β5i and PA28α, although it decreases the 20S constitutive proteasome subunits (α2, β5). Ethanol also upregulates mTOR phosphorylation, leading to a downregulation of the autophagy-lysosome pathway (ATG12, ATG5, cathepsin B, p62, LC3) and alters the volume of autophagic vacuoles. Notably, mice lacking TLR4 receptors are protected against ethanol-induced alterations in protein degradation pathways. In summary, the present results provide the first evidence demonstrating that chronic ethanol treatment causes proteolysis dysfunctions in the mouse cerebral cortex and that these events are TLR4 dependent. These findings could provide insight into the mechanisms underlying ethanol-induced brain damage.
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