ArticleCell2022
The Parkinson's disease protein alpha-synuclein is a modulator of processing bodies and mRNA stability.
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Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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108citing papers in PubMed
18.4field-weighted citation impact, top 1% of its field
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108 citing papers in PubMed, 157 citations in OpenAlex.
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- ACE2 and Parkinsonism‑related bone metabolic alterations: signaling pathways and hub gene analysis.Molecular genetics and genomics : MGG · 2026Article
- Cholesterol dysregulation in APOE4 astrocytes promotes α-synuclein pathology in miBrains.Cell stem cell · 2026Article
- Selective RNA sequestration in biomolecular condensates directs cell fate transitions.Nature biotechnology · 2026Article
- RNA Promotes Synapsin Condensates That Organize Synaptic Vesicles in Live Neurons and Enable Localized Translation in Reconstituted System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- α-Synuclein blocks endoplasmic reticulum co-translational protein translocation early in Parkinson's disease.Nature communications · 2026Article
- Modeling Parkinson's pathology in human iPSC dopaminergic neurons uncovers key mechanisms of Lewy body formation and heterogeneity.Science advances · 2026Article
- NERINE reveals rare variant associations in gene networks across phenotypes and implicates an SNCA-PRL-LRRK2 subnetwork in Parkinson's disease.Cell genomics · 2026Article
- iSCORE-PD: an isogenic stem cell collection to research Parkinson's disease.Nature communications · 2026Article
- Article
- Determination of α-Synuclein Protein Interactions by μMap Photoproximity Labeling.Journal of the American Chemical Society · 2026Article
- WDR44 drives de novo α-synuclein aggregation at the lysosomal membrane and promotes neuronal dysfunction in Parkinson's Disease.bioRxiv : the preprint server for biology · 2026Article
- Alpha-Synuclein in Neurodegeneration: From Shared Biology to Disease-Specific Phenotypes.Cells · 2026Review
- RNA promotes synapsin phase separation providing a platform for local translation.bioRxiv : the preprint server for biology · 2026Article
- A split biotin ligase approach reveals proteins associated with oligomeric alpha-synuclein during aggregation.Scientific reports · 2026Article
- Disrupting Lipid Raft Microdomains to Block Polyploid Giant Cancer Cell Budding and Enhance Radiotherapy Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.Genome biology · 2026Review
- PhaSepDB 3.0: a comprehensive knowledgebase of phase separation-related proteins from AI-assisted curation.Nucleic acids research · 2026Article
- ZDHHC5 interacts physically and functionally with DLG1 at primary cilia and regulates ciliary length and kidney morphology.Frontiers in cell and developmental biology · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
48 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 13 institutions in 2 countries.
Erinc HallacliAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Can KayatekinWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Sumaiya NazeenAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Xiou H WangAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Zoe SheinkopfAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Shubhangi SathyakumarAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Souvarish SarkarDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Xin JiangYumanity Therapeutics, Boston, MA 02135, USA.
Xianjun DongAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Genomics and Bioinformatics Hub, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
Roberto Di MaioPittsburgh Institute for Neurodegenerative Diseases and Department of Neurology, Pittsburgh, PA 15213, USA.
Wen WangDepartment of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Matthew T KeeneyPittsburgh Institute for Neurodegenerative Diseases and Department of Neurology, Pittsburgh, PA 15213, USA.
Daniel FelskyKrembil Centre for Neuroinformatics and Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON M5T 3M7, Canada.
Jackson SandoeWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Aazam VahdatshoarAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Namrata D UdeshiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
D R ManiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Steven A CarrBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Susan LindquistWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Cambridge, MA 02142, USA; Department of Biology, MIT, Cambridge, MA 02139, USA.
Philip L De JagerCenter for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
David P BartelWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Cambridge, MA 02142, USA; Department of Biology, MIT, Cambridge, MA 02139, USA.
Chad L MyersDepartment of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
J Timothy GreenamyrePittsburgh Institute for Neurodegenerative Diseases and Department of Neurology, Pittsburgh, PA 15213, USA.
Mel B FeanyDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Shamil R SunyaevDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Chee Yeun ChungYumanity Therapeutics, Boston, MA 02135, USA.
Vikram KhuranaAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: vkhurana@bwh.harvard.edu.
Brigham and Women's Hospital · USBroad Institute · USInstitute for Neurodegenerative Disorders · USWhitehead Institute for Biomedical Research · USHarvard University · USUniversity of Minnesota · USYumanity Therapeutics (United States) · USCanada Research Chairs · CAColumbia University Irving Medical Center · USHarvard Stem Cell Institute · USHoward Hughes Medical Institute · USIIT@MIT · USResearch Network (United States) · US
Funding
Statistical methods for studies of rare variantsR01MH101244 · NIMH · HARVARD MEDICAL SCHOOL · PI Benjamin Michael Neale, ALKES L PRICE · 2013 to 2026
$9.4MThe origin, the function and the phenotypic impact of human allelesR35GM127131 · NIGMS · HARVARD MEDICAL SCHOOL · PI SHAMIL SUNYAEV · 2018 to 2026
$8.1MElucidating the Biological Differences Between Distinct Fibrillar and Non-Fibrillar Alpha-Synuclein Inclusions in Human Stem-Cell ModelsR01NS109209 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KHURANA, VIKRAM · 2020 to 2024
$4.5MMechanistic dissection of P-body formation and abnormal mRNA degradation in alpha-synucleinopathyR21NS112858 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KHURANA, VIKRAM · 2019 to 2019
$492kNIGMS NIH HHS R35 GM127131NIMH NIH HHS R01 MH101244NINDS NIH HHS R01 NS109209NINDS NIH HHS R21 NS112858
Abstract
Alpha-synuclein (αS) is a conformationally plastic protein that reversibly binds to cellular membranes. It aggregates and is genetically linked to Parkinson's disease (PD). Here, we show that αS directly modulates processing bodies (P-bodies), membraneless organelles that function in mRNA turnover and storage. The N terminus of αS, but not other synucleins, dictates mutually exclusive binding either to cellular membranes or to P-bodies in the cytosol. αS associates with multiple decapping proteins in close proximity on the Edc4 scaffold. As αS pathologically accumulates, aberrant interaction with Edc4 occurs at the expense of physiologic decapping-module interactions. mRNA decay kinetics within PD-relevant pathways are correspondingly disrupted in PD patient neurons and brain. Genetic modulation of P-body components alters αS toxicity, and human genetic analysis lends support to the disease-relevance of these interactions. Beyond revealing an unexpected aspect of αS function and pathology, our data highlight the versatility of conformationally plastic proteins with high intrinsic disorder.
Indexed as
alpha-SynucleinParkinson DiseaseHumansProcessing BodiesProteinsRNA Stabilityalpha-SynucleinEDC4 protein, humanProteinsalpha-synucleiniPSCLewy body diseasemRNA degradationmRNA stabilityParkinson's diseaseProcessing bodiesrare variantRNA-binding proteinssynucleinopathy
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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 Socratic graph.