ArticleNPJ Parkinson's disease2023
C/EBPβ/AEP is age-dependently activated in Parkinson's disease and mediates α-synuclein in the gut and brain.
Article in NPJ Parkinson's disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- C/EBPβ as a master regulator of inflammasome signaling in neurodegenerative diseases: mechanisms and therapeutic implications.Frontiers in immunology · 2025Pooled it
- C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Pooled it
- C/EBPβ Drives Ischemia-Induced Microglial Inflammatory Reprogramming Through Transcriptional Activation of ATF3 and Exacerbates Brain Injury.Molecular neurobiology · 2026Article
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- The Brain-Gut Axis in Parkinson's Disease Pathology.Comprehensive Physiology · 2026Review
- Gut microbiota and Parkinson's disease: exploring pathogenesis and potential therapeutic strategies from a gut-brain axis perspective.iScience · 2026Review
- Identification of Gene Signatures and Molecular Mechanisms for Diagnosing Parkinson's Disease and Nonalcoholic Fatty Liver Disease Using Machine Learning.Parkinson's disease · 2026Article
- An update on the involvement of inflammatory mediators in Parkinson's disease pathogenesis.Archives of toxicology · 2025Review
- Gut Microbiota-Based Interventions for Parkinson's Disease: Neuroprotective Mechanisms and Current Perspective.Probiotics and antimicrobial proteins · 2025Review
- A hypothesis explaining Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies overlap.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Disruption of axonal transport in Parkinson's disease: the role of pathological α-Syn and AMPK/p38 MAPK signaling.NPJ Parkinson's disease · 2025Article
- Alpha synuclein and inflammaging.Heliyon · 2025Review
- Roles of C/EBPβ/AEP in Neurodegenerative Diseases.Current topics in medicinal chemistry · 2025Review
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- Inflammatory Intracellular Signaling in Neurons Is Influenced by Glial Soluble Factors in iPSC-Based Cell Model ofInternational journal of molecular sciences · 2024Article
- High pulse wave velocity is associated with enlarged perivascular spaces in dementia with Lewy bodies.Scientific reports · 2024Article
- Relationship Between Short-chain Fatty Acids and Parkinson's Disease: A Review from Pathology to Clinic.Neuroscience bulletin · 2024Review
- Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is the most common neurodegenerative motor disorder, and its pathologic hallmarks include extensive dopaminergic neuronal degeneration in the Substantia nigra associated with Lewy bodies, predominantly consisting of phosphorylated and truncated α-Synuclein (α-Syn). Asparagine endopeptidase (AEP) cleaves human α-Syn at N103 residue and promotes its aggregation, contributing to PD pathogenesis. However, how AEP mediates Lewy body pathologies during aging and elicits PD onset remains incompletely understood. Knockout of AEP or C/EBPβ from α-SNCA mice, and their chronic rotenone exposure models were used, and the mechanism of α-Syn from the gut that spread to the brain was observed. Here we report that C/EBPβ/AEP pathway, aggravated by oxidative stress, is age-dependently activated and cleaves α-Syn N103 and regulates Lewy body-like pathologies spreading from the gut into the brain in human α-SNCA transgenic mice. Deletion of C/EBPβ or AEP substantially diminished the oxidative stress, neuro-inflammation, and PD pathologies, attenuating motor dysfunctions in aged α-SNCA mice. Noticeably, PD pathologies initiate in the gut and progressively spread into the brain. Chronic gastric exposure to a low dose of rotenone initiates Lewy body-like pathologies in the gut that propagate into the brain in a C/EBPβ/AEP-dependent manner. Hence, our studies demonstrate that C/EBPβ/AEP pathway is critical for mediating Lewy body pathology progression in PD.
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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.