ArticleActa neuropathologica2016
Proaggregant nuclear factor(s) trigger rapid formation of α-synuclein aggregates in apoptotic neurons.
Article in Acta neuropathologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed.
- Nuclear alpha-synuclein accelerates cell senescence and neurodegeneration.Immunity & ageing : I & A · 2024Article
- Cerebral Microvascular Injury Induced by Lag3-Dependent α-Synuclein Fibril Endocytosis Exacerbates Cognitive Impairment in a Mouse Model of α-Synucleinopathies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Review
- Aggregated Alpha-Synuclein Inclusions within the Nucleus Predict Impending Neuronal Cell Death in a Mouse Model of Parkinsonism.International journal of molecular sciences · 2022Article
- Constitutive nuclear accumulation of endogenous alpha-synuclein in mice causes motor impairment and cortical dysfunction, independent of protein aggregation.Human molecular genetics · 2022Article
- Lipid Nanoparticles: Promising Treatment Approach for Parkinson's Disease.International journal of molecular sciences · 2022Review
- Article
- Neuropathology and molecular diagnosis of Synucleinopathies.Molecular neurodegeneration · 2021Review
- Pathologic tau conformer ensembles induce dynamic, liquid-liquid phase separation events at the nuclear envelope.BMC biology · 2021Article
- Apoptotic Neuron-Derived Histone Amyloid Fibrils Induce α-Synuclein Aggregation.Molecular neurobiology · 2021Article
- MicroRNA Dysregulation in Parkinson's Disease: A Narrative Review.Frontiers in neuroscience · 2021Review
- The mechanistic role of alpha-synuclein in the nucleus: impaired nuclear function caused by familial Parkinson's disease SNCA mutations.Human molecular genetics · 2020Article
- The Nuclear Lamina: Protein Accumulation and Disease.Biomedicines · 2020Review
- Cellular Biology of Tau Diversity and Pathogenic Conformers.Frontiers in neurology · 2020Review
- Neuropathology and pathogenesis of extrapyramidal movement disorders: a critical update-I. Hypokinetic-rigid movement disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2019Review
- Sensitivity and specificity of phospho-Ser129 α-synuclein monoclonal antibodies.The Journal of comparative neurology · 2018Article
- Parkinson's disease: experimental models and reality.Acta neuropathologica · 2018Review
- Neuropathology of Parkinson disease.Parkinsonism & related disorders · 2018Review
- Impaired endo-lysosomal membrane integrity accelerates the seeding progression of α-synuclein aggregates.Scientific reports · 2017Article
- Histones facilitate α-synuclein aggregation during neuronal apoptosis.Acta neuropathologica · 2017Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Cell-to-cell transmission of α-synuclein (αS) aggregates has been proposed to be responsible for progressive αS pathology in Parkinson disease (PD) and related disorders, including dementia with Lewy bodies. In support of this concept, a growing body of in vitro and in vivo experimental evidence shows that exogenously introduced αS aggregates can spread into surrounding cells and trigger PD-like pathology. It remains to be determined what factor(s) lead to initiation of αS aggregation that is capable of seeding subsequent propagation. In this study we demonstrate that filamentous αS aggregates form in neurons in response to apoptosis induced by staurosporine or other toxins-6-hydroxy-dopamine and 1-methyl-4-phenylpyridinium (MPP+). Interaction between αS and proaggregant nuclear factor(s) is associated with disruption of nuclear envelope integrity. Knocking down a key nuclear envelop constituent protein, lamin B1, enhances αS aggregation. Moreover, in vitro and in vivo experimental models demonstrate that aggregates released upon cell breakdown can be taken up by surrounding cells. Accordingly, we suggest that at least some αS aggregation might be related to neuronal apoptosis or loss of nuclear membrane integrity, exposing cytosolic α-synuclein to proaggregant nuclear factors. These findings provide new clues to the pathogenesis of PD and related disorders that can lead to novel treatments of these disorders. Specifically, finding ways to limit the effects of apoptosis on αS aggregation, deposition, local uptake and subsequent propagation might significantly impact progression of disease.
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