ArticlePloS one2017
The ER retention protein RER1 promotes alpha-synuclein degradation via the proteasome.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 25 citations in OpenAlex.
- Rab8a dysregulation in Parkinson's disease: A convergence of genetic and molecular pathologies.Molecular biology reports · 2026Review
- Ubiquitin chain variability directs substrates of the Tul1 ubiquitin ligase complex to different degradation pathways.The Journal of cell biology · 2025Article
- Review
- RER1 regulates lipid metabolism in monocytes and macrophages.Cellular and molecular life sciences : CMLS · 2025Article
- Review
- From lab bench to hope: a review of gene therapies in clinical trials for Parkinson's disease and challenges.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Review
- Review
- Cellular turnover and degradation of the most common missense cystathionine beta-synthase variants causing homocystinuria.Protein science : a publication of the Protein Society · 2024Article
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Chemoproteomic-enabled characterization of small GTPase Rab1a as a target of anRSC chemical biology · 2022Article
- Nedd4-2 Haploinsufficiency in Mice Impairs the Ubiquitination of Rer1 and Increases the Susceptibility to Endoplasmic Reticulum Stress and Seizures.Frontiers in molecular neuroscience · 2022Article
- Alpha-Synuclein FRET Biosensors Reveal Early Alpha-Synuclein Aggregation in the Endoplasmic Reticulum.Life (Basel, Switzerland) · 2020Article
- Protein-Protein Interactions in Alpha-Synuclein Biogenesis: New Potential Targets in Parkinson's Disease.Frontiers in aging neuroscience · 2020Article
- Congrong Shujing Granule-Induced GRP78 Expression Reduced Endoplasmic Reticulum Stress and Neuronal Apoptosis in the Midbrain in a Parkinson's Disease Rat Model.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- α-Synuclein in Parkinson's disease: causal or bystander?Journal of neural transmission (Vienna, Austria : 1996) · 2019Review
- RER1 enhances carcinogenesis and stemness of pancreatic cancer under hypoxic environment.Journal of experimental & clinical cancer research : CR · 2019Article
- Alpha-Synuclein Physiology and Pathology: A Perspective on Cellular Structures and Organelles.Frontiers in neuroscience · 2019Review
- Ttyh1 regulates embryonic neural stem cell properties by enhancing the Notch signaling pathway.EMBO reports · 2018Article
- New Perspectives on Roles of Alpha-Synuclein in Parkinson's Disease.Frontiers in aging neuroscience · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Abnormal accumulation of α-synuclein (αSyn) has been linked to endoplasmic-reticulum (ER) stress, defective intracellular protein/vesicle trafficking, and cytotoxicity. Targeting factors involved in ER-related protein processing and trafficking may, therefore, be a key to modulating αSyn levels and associated toxicity. Recently retention in endoplasmic reticulum 1 (RER1) has been identified as an important ER retrieval/retention factor for Alzheimer's disease proteins and negatively regulates amyloid-β peptide levels. Here, we hypothesized that RER1 might also play an important role in retention/retrieval of αSyn and mediate levels. We expressed RER1 and a C-terminal mutant RER1Δ25, which lacks the ER retention/retrieval function, in HEK293 and H4 neuroglioma cells. RER1 overexpression significantly decreased levels of both wild type and A30P, A53T, and E46K disease causal mutants of αSyn, whereas the RER1Δ25 mutant had a significantly attenuated effect on αSyn. RER1 effects were specific to αSyn and had little to no effect on either βSyn or the Δ71-82 αSyn mutant, which both lack the NAC domain sequence critical for synuclein fibrillization. Tests with proteasomal and macroautophagy inhibitors further demonstrate that RER1 effects on αSyn are primarily mediated through the ubiquitin-proteasome system. RER1 also appears to interact with the ubiquitin ligase NEDD4. RER1 in human diseased brain tissues co-localizes with αSyn-positive Lewy bodies. Together, these findings provide evidence that RER1 is a novel and potential important mediator of elevated αSyn levels. Further investigation of the mechanism of RER1 and downstream effectors on αSyn may yield novel therapeutic targets for modulation in Parkinson disease and related synucleinopathies.
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.