ArticleInternational journal of molecular sciences2021
TRAIL Mediates Neuronal Death in AUD: A Link between Neuroinflammation and Neurodegeneration.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- Pro-inflammatory microglia drive escalated alcohol consumption during early abstinence.bioRxiv : the preprint server for biology · 2026Article
- Repeated TLR7 activation induces cell type- and brain region-specific transcriptome changes in male mice.Scientific reports · 2026Article
- The Immuno-Glial Connectome in Alzheimer's Disease: Integrating Central and Peripheral Inflammatory Networks.Cellular and molecular neurobiology · 2026Review
- Microglia Promote Neurodegeneration and Hyperkatifeia during Withdrawal and Abstinence from Binge Alcohol.The American journal of pathology · 2026Article
- Neurotoxicity of Chronic Alcohol Exposure: Mechanistic Insights, Cellular Disruption, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Microglia promote neurodegeneration and hyperkatifeia during withdrawal and prolonged abstinence from binge alcohol.bioRxiv : the preprint server for biology · 2025Article
- The Neuropathology of Alcohol Use Disorder: Cellular Insights From Human Post-Mortem Studies.Journal of neurochemistry · 2025Review
- Alcohol consumption in P301S mice accelerates gait impairments, modifies aggregation of pathological tau and alters microglia within the hippocampus.Alcohol, clinical & experimental research · 2025Article
- Loss of lysosomal acid lipase contributes to Alzheimer's disease pathology and cognitive decline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Excessive Alcohol Use as a Risk Factor for Alzheimer's Disease: Epidemiological and Preclinical Evidence.Advances in experimental medicine and biology · 2025Review
- Microglia either promote or restrain TRAIL-mediated excitotoxicity caused by AβJournal of neuroinflammation · 2024Article
- Toll-like receptor 7: A novel neuroimmune target to reduce excessive alcohol consumption.Neurobiology of stress · 2024Article
- Binge ethanol exposure in advanced age elevates neuroinflammation and early indicators of neurodegeneration and cognitive impairment in female mice.Brain, behavior, and immunity · 2024Article
- Causal relationship between inflammatory factors and cerebral small vessel disease: Univariate, multivariate, and summary-data-based mendelian randomization analysis.Brain and behavior · 2024Article
- Die Hard: Necroptosis and its Impact on Age-Dependent Neuroinflammatory Diseases.Frontiers in cell death · 2024Article
- Epigenetic regulation of microglia and neurons by proinflammatory signaling following adolescent intermittent ethanol (AIE) exposure and in human AUD.Advances in drug and alcohol research · 2024Review
- Alcohol, HMGB1, and Innate Immune Signaling in the Brain.Alcohol research : current reviews · 2024Review
- Detrimental Effects of Alcohol-Induced Inflammation on Brain Health: From Neurogenesis to Neurodegeneration.Cellular and molecular neurobiology · 2023Review
- Targeting Persistent Changes in Neuroimmune and Epigenetic Signaling in Adolescent Drinking to Treat Alcohol Use Disorder in Adulthood.Pharmacological reviews · 2023Review
- Emerging Links between Nonalcoholic Fatty Liver Disease and Neurodegeneration.Seminars in liver disease · 2023Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Although the cause of progressive neurodegeneration is often unclear, neuronal death can occur through several mechanisms. In conditions such as Alzheimer's or alcohol use disorder (AUD), Toll-like receptor (TLR) induction is observed with neurodegeneration. However, links between TLR activation and neurodegeneration are lacking. We report a role of apoptotic neuronal death in AUD through TLR7-mediated induction of death receptor signaling. In postmortem human cortex, a two-fold increase in apoptotic terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining in neurons was found in AUD versus controls. This occurred with the increased expression of TLR7 and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) death receptors. Binge ethanol treatment in C57BL/6 mice increased TLR7 and induced neuronal apoptosis in cortical regions that was blocked by TLR7 antagonism. Mechanistic studies in primary organotypic brain slice culture (OBSC) found that the inhibition of TLR7 and its endogenous ligand let-7b blocked ethanol-induced neuronal cell death. Both IMQ and ethanol induced the expression of TRAIL and its death receptor. In addition, TRAIL-neutralizing monoclonal antibodies blocked both imiquimod (IMQ) and ethanol induced neuronal death. These findings implicate TRAIL as a mediator of neuronal apoptosis downstream of TLR7 activation. TLR7 and neuronal apoptosis are implicated in other neurodegenerative diseases, including Alzheimer's disease. Therefore, TRAIL may represent a therapeutic target to slow neurodegeneration in multiple diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.