ArticleNature communications2015
Parkinson-causing α-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 213 papers.
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Who cites it
213 citing papers in PubMed, 304 citations in OpenAlex.
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Quantifying the Acute Toxicity of Alpha-Synuclein Membrane-Accumulation in a Cell-Based Assay.Journal of molecular neuroscience : MN · 2026Article
- Lipid droplets promote aberrant liquid-liquid phase separation of alpha-synuclein impairing energy homeostasis.EMBO reports · 2026Article
- Elevation of Stearoyl-Coenzyme A Desaturase and Monounsaturated Fatty Acids in Parkinson's Disease Serum.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Large-scale visualization of α-synuclein oligomers in Parkinson's disease brain tissue.Nature biomedical engineering · 2026Article
- The Emerging Parkinson's Disease Oxylipin-Ome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Incense Aerosol-Induced Neurotoxicity Disrupts α-Synuclein Homeostasis in a Cellular Parkinson's Disease Model, Distinct from Cigarette Aerosols.Chemical research in toxicology · 2026Article
- Lipid membrane remodeling by myristic acid treatment reverses Parkinson's disease α-synuclein phenotypes in patient neurons.npj metabolic health and disease · 2026Article
- Tubulin transforms Tau and α-synuclein condensates from pathological to physiological.Nature communications · 2026Article
- Investigating the efficacy, methods, and challenges of induced pluripotent stem cells (iPSC) therapy in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Quantifying the Acute Toxicity of Alpha-Synuclein Membrane-Accumulation in a Cell-Based Assay.Research square · 2026Article
- When Proteins Go MAD-Misfolded, Amplified, Detected: Advances in α-Synuclein Pathophysiology and RT-QuIC Detection.Molecular neurobiology · 2026Review
- Parkinson's disease-specific α-Synuclein variants potentially drive Lewy body formation by engaging in promiscuous and non-functional interactions.Communications biology · 2026Article
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- Disrupting α-Synuclein-ClpP interaction restores mitochondrial function and attenuates neuropathology in Parkinson's disease models.Molecular neurodegeneration · 2025Article
- Synaptic Vesicle Disruption in Parkinson's Disease: Dual Roles of α-Synuclein and Emerging Therapeutic Targets.Brain sciences · 2025Review
- Lipid droplets promote the aberrant liquid-liquid phase separation of alpha-synuclein leading to impaired energy homeostasis.bioRxiv : the preprint server for biology · 2025Article
- Parkinson disease is a fatty acidopathy.Nature reviews. Neurology · 2025Review
- ZnJournal of the American Chemical Society · 2025Article
- Acute introduction of monomeric or multimeric α-synuclein induces distinct impacts on synaptic vesicle trafficking at lamprey giant synapses.The Journal of physiology · 2025Article
153 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
β-Sheet-rich α-synuclein (αS) aggregates characterize Parkinson's disease (PD). αS was long believed to be a natively unfolded monomer, but recent work suggests it also occurs in α-helix-rich tetramers. Crosslinking traps principally tetrameric αS in intact normal neurons, but not after cell lysis, suggesting a dynamic equilibrium. Here we show that freshly biopsied normal human brain contains abundant αS tetramers. The PD-causing mutation A53T decreases tetramers in mouse brain. Neurons derived from an A53T patient have decreased tetramers. Neurons expressing E46K do also, and adding 1-2 E46K-like mutations into the canonical αS repeat motifs (KTKEGV) further reduces tetramers, decreases αS solubility and induces neurotoxicity and round inclusions. The other three fPD missense mutations likewise decrease tetramer:monomer ratios. The destabilization of physiological tetramers by PD-causing missense mutations and the neurotoxicity and inclusions induced by markedly decreasing tetramers suggest that decreased α-helical tetramers and increased unfolded monomers initiate pathogenesis. Tetramer-stabilizing compounds should prevent this.
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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 OpenQuestion graph.