ArticleActa neuropathologica2012
Aggregation of αSynuclein promotes progressive in vivo neurotoxicity in adult rat dopaminergic neurons.
Article in Acta neuropathologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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
57 citing papers in PubMed, 97 citations in OpenAlex.
- Dissecting the Molecular Determinants of α-synuclein Phase Separation and Condensate Aging: The Pivotal Role of β-Sheet-Rich Motifs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neurotoxicology of dopamine: Victim or assailant?Neurotoxicology · 2024Review
- Nonintuitive Immunogenicity and Plasticity of Alpha-Synuclein Conformers: A Paradigm for Smart Delivery of Neuro-Immunotherapeutics.Pharmaceutics · 2024Review
- Assessment of the Anti-Amyloidogenic Properties of Essential Oils and Their Constituents in Cells Using a Whole-Cell Recombinant Biosensor.Brain sciences · 2023Article
- From cradle to grave: neurogenesis, neuroregeneration and neurodegeneration in Alzheimer's and Parkinson's diseases.Neural regeneration research · 2022Review
- Small soluble α-synuclein aggregates are the toxic species in Parkinson's disease.Nature communications · 2022Article
- α-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox.Cell & bioscience · 2021Review
- Observation of an α-synuclein liquid droplet state and its maturation into Lewy body-like assemblies.Journal of molecular cell biology · 2021Article
- Adeno-Associated Virus Expression of α-Synuclein as a Tool to Model Parkinson's Disease: Current Understanding and Knowledge Gaps.Aging and disease · 2021Review
- Single-Molecule Counting Coupled to Rapid Amplification Enables Detection of α-Synuclein Aggregates in Cerebrospinal Fluid of Parkinson's Disease Patients.Angewandte Chemie (International ed. in English) · 2021Article
- Low-Expressing Synucleinopathy Mouse Models Based on Oligomer-Forming Mutations and C-Terminal Truncation of α-Synuclein.Frontiers in neuroscience · 2021Article
- Dysregulation of MicroRNAs and PIWI-Interacting RNAs in aFrontiers in neuroscience · 2021Article
- A method of purifying alpha-synuclein inHeliyon · 2021Article
- Anti-aggregation Effects of Phenolic Compounds on α-synuclein.Molecules (Basel, Switzerland) · 2020Review
- Inhibition of HDAC6 activity protects dopaminergic neurons from alpha-synuclein toxicity.Scientific reports · 2020Article
- The function of bacterial HtrA is evolutionally conserved in mammalian HtrA2/Omi.Scientific reports · 2020Article
- The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Modeling Parkinson's Disease With the Alpha-Synuclein Protein.Frontiers in pharmacology · 2020Review
- Pathogenic Mutations Differentially Regulate Cell-to-Cell Transmission of α-Synuclein.Frontiers in cellular neuroscience · 2020Article
- Homogenous generation of dopaminergic neurons from multiple hiPSC lines by transient expression of transcription factors.Cell death & disease · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibrillar αSynuclein is the major constituent of Lewy bodies and Lewy neurites, the protein deposits characteristic for Parkinson's disease (PD). Multiplications of the αSynuclein gene, as well as point mutations cause familial PD. However, the exact role of αSynuclein in neurodegeneration remains uncertain. Recent research in invertebrates has suggested that oligomeric rather than fibrillizing αSynuclein mediates neurotoxicity. To investigate the impact of αSynuclein aggregation on the progression of neurodegeneration, we expressed variants with different fibrillation propensities in the rat substantia nigra (SN) by means of recombinant adeno-associated viral (AAV) vectors. The formation of proteinase K-resistant αSynuclein aggregates was correlated to the loss of nigral dopaminergic (DA) neurons and striatal fibers. Expression of two prefibrillar, structure-based design mutants of αSynuclein (i.e., A56P and A30P/A56P/A76P) resulted in less aggregate formation in nigral DA neurons as compared to human wild-type (WT) or the inherited A30P mutation. However, only the αSynuclein variants capable of forming fibrils (WT/A30P), but not the oligomeric αSynuclein species induced a sustained progressive loss of adult nigral DA neurons. These results demonstrate that divergent modes of αSynuclein neurotoxicity exist in invertebrate and mammalian DA neurons in vivo and suggest that fibrillation of αSynuclein promotes the progressive degeneration of nigral DA neurons as found in PD patients.
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.