ArticleNeuron2022
Rescue of α-synuclein aggregation in Parkinson's patient neurons by synergistic enhancement of ER proteostasis and protein trafficking.
Article in Neuron, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Meta-analysis and in-silico functional characterization of the SNCA variant rs356220 in Parkinson's disease.Scientific reports · 2025Pooled it
- The Reductive Stress Nexus: Integrated Pathways of Metabolic Dysregulation, Senescence and Blood-Brain Barrier Failure in Neurodegenerative Disease and Brain Aging.Cell biochemistry and biophysics · 2026Review
- Olfactory proteomics reveals the capacity of the HDAC1 inhibitor pyroxamide to halt the α-synuclein preformed fibrils-induced damage in nasal epithelial, microglial and dopaminergic neuronal cell lines.Brain pathology (Zurich, Switzerland) · 2026Article
- Long-Term Impact of Historical BCG Vaccination Policies on Parkinson's Disease Risk: A Hypothesis-Generating Retrospective Cohort Analysis.Biomedicines · 2026Article
- α-Synuclein blocks endoplasmic reticulum co-translational protein translocation early in Parkinson's disease.Nature communications · 2026Article
- Large-scale bidirectional arrayed genetic screens identify OXR1 and EMC4 as modifiers of αSynuclein aggregation.FEBS open bio · 2026Article
- Malformin A1-mediated cytotoxicity in ovarian cancer cells occurs through pyroptosis and autophagy.FEBS open bio · 2026Article
- Spatial multi-omics reveals region-specific molecular signatures in a 6-OHDA model of Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Engineered neuronal exosomes mediate α-synuclein clearance to ameliorate Parkinson's disease.Journal of nanobiotechnology · 2026Article
- Article
- TNF alpha unmasks enteric malate aspartate shuttle dysfunction bridging Parkinson disease and intestinal inflammation.Nature communications · 2026Article
- The diverse forms and roles of the neuronal endoplasmic reticulum.Nature reviews. Neuroscience · 2026Review
- In Vivo Screen of Parkinson's Disease GWAS Risk Genes IdentifiesThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Single-cell transcriptomics revealed molecular vulnerability in a human midbrain-like organoid model of Parkinson's disease.iScience · 2026Article
- SNCA triplication disrupts proteostasis and extracellular architecture prior to neurodegeneration in human midbrain organoids.NPJ Parkinson's disease · 2026Article
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Environmental noise-induced changes to the IC-SNc circuit promotes motor deficits and neuronal vulnerability in a mouse model of Parkinson's Disease.PLoS biology · 2025Article
- Inborn errors of canonical autophagy in neurodegenerative diseases.Human molecular genetics · 2025Review
- Two-Color Timestamping of Gene Expression with a Chemigenetic Reporter System.Chembiochem : a European journal of chemical biology · 2025Article
- The quest for Parkinson's disease biomarkers: traditional and emerging multi-omics approaches.Molecular biology reports · 2025Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Neurodegenerative disorders are characterized by a collapse in proteostasis, as shown by the accumulation of insoluble protein aggregates in the brain. Proteostasis involves a balance of protein synthesis, folding, trafficking, and degradation, but how aggregates perturb these pathways is unknown. Using Parkinson's disease (PD) patient midbrain cultures, we find that aggregated α-synuclein induces endoplasmic reticulum (ER) fragmentation and compromises ER protein folding capacity, leading to misfolding and aggregation of immature lysosomal β-glucocerebrosidase. Despite this, PD neurons fail to initiate the unfolded protein response, indicating perturbations in sensing or transducing protein misfolding signals in the ER. Small molecule enhancement of ER proteostasis machinery promotes β-glucocerebrosidase solubility, while simultaneous enhancement of trafficking improves ER morphology, lysosomal function, and reduces α-synuclein. Our studies suggest that aggregated α-synuclein perturbs the ability of neurons to respond to misfolded proteins in the ER, and that synergistic enhancement of multiple proteostasis branches may provide therapeutic benefit 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.