ArticleActa pharmacologica Sinica2022
HACE1 negatively regulates neuroinflammation through ubiquitylating and degrading Rac1 in Parkinson's disease models.
Article in Acta pharmacologica Sinica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Adipocyte-derived exosomal miR-27a-3p promotes macrophage M1 polarization via HACE1/RAC1/STAT3 axis to exacerbate the progression of childhood asthma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Deltex 2 Mediates Oxidative Stress and Neurotoxicity in Freezing of Gait of Parkinson's Disease via the Notch2-Nrf2 Axis.CNS neuroscience & therapeutics · 2026Article
- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- Anti-Apoptotic Effects of Escin on Porphyromonas gingivalis-Derived Lipopolysaccharide-Induced Injury in SH-SY5Y Cells.Brain and behavior · 2025Article
- Immune cell metabolic dysfunction in Parkinson's disease.Molecular neurodegeneration · 2025Review
- Shared interactions of six neurotropic viruses with 38 human proteins: a computational and literature-based exploration of viral interactions and hijacking of human proteins in neuropsychiatric disorders.Discover mental health · 2025Article
- HACE1 as a bridge between oxidative stress and autophagy.Frontiers in immunology · 2025Review
- Exploring the Role of Ubiquitin-Proteasome System in the Pathogenesis of Parkinson's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Expression of USP25 associates with fibrosis, inflammation and metabolism changes in IgG4-related disease.Nature communications · 2024Article
- Common cytokine receptor gamma chain family cytokines activate MAPK, PI3K, and JAK/STAT pathways in microglia to influence Alzheimer's Disease.Frontiers in molecular neuroscience · 2024Article
- Inhibition of esophageal cancer progression through HACE1-TRIP12 interaction and associated RAC1 ubiquitination and degradation.Journal of Cancer · 2024Article
- JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions.Molecular biomedicine · 2023Review
- Hace1 overexpression mitigates myocardial hypoxia/reoxygenation injury via the effects on Keap1/Nrf2 pathway.In vitro cellular & developmental biology. Animal · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroinflammation plays an important role in neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease. HACE1 (HECT domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1) is a tumor suppressor. Recent evidence suggests that HACE1 may be involved in oxidative stress responses. Due to the critical role of ROS in neuroinflammation, we speculated that HACE1 might participate in neuroinflammation and related neurodegenerative diseases, such as PD. In this study, we investigated the role of HACE1 in neuroinflammation of PD models. We showed that HACE1 knockdown exacerbated LPS-induced neuroinflammation in BV2 microglial cells in vitro through suppressing ubiquitination and degradation of activated Rac1, an NADPH oxidase subunit. Furthermore, we showed that HACE1 exerted vital neuronal protection through increasing Rac1 activity and stability in LPS-treated SH-SY5Y cells, as HACE1 knockdown leading to lower tolerance to LPS challenge. In MPTP-induced acute PD mouse model, HACE1 knockdown exacerbated motor deficits by activating Rac1. Finally, mutant α-synuclein (A53T)-overexpressing mice, a chronic PD mouse model, exhibited age-dependent reduction of HACE1 levels in the midbrain and striatum, implicating that HACE1 participated in PD pathological progression. This study for the first time demonstrates that HACE1 is a negative regulator of neuroinflammation and involved in the PD pathogenesis by regulating Rac1 activity. The data support HACE1 as a potential target for PD and other neurodegenerative diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.