ArticleHuman molecular genetics2022
Constitutive nuclear accumulation of endogenous alpha-synuclein in mice causes motor impairment and cortical dysfunction, independent of protein aggregation.
Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 76 citations in OpenAlex.
- Establishment and Characterization of Behavioral Changes in the Nuclear Localization Human α-Synuclein Transgenic Mice.Diseases (Basel, Switzerland) · 2025Article
- Structural and functional insights into the nuclear role of Parkinson's disease-associated α-synuclein as a histone chaperone.Communications biology · 2025Article
- A stress-dependent TDP-43 SUMOylation program preserves neuronal function.Molecular neurodegeneration · 2025Article
- A reciprocal relationship between markers of genomic DNA damage and alpha-synuclein pathology in dementia with Lewy bodies.Molecular neurodegeneration · 2025Article
- Hypoxia-inducible factor-1 as targets for neuroprotection : from ferroptosis to Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- The nuclear envelope and nuclear pore complexes in neurodegenerative diseases.Frontiers in cell and developmental biology · 2025Review
- Nuclear pore and nucleocytoplasmic transport impairment in oxidative stress-induced neurodegeneration: relevance to molecular mechanisms in Pathogenesis of Parkinson's and other related neurodegenerative diseases.Molecular neurodegeneration · 2024Review
- Alpha-synuclein modulates the repair of genomic DNA double-strand breaks in a DNA-PKNeurobiology of disease · 2024Article
- Genetic and pharmacological reduction of CDK14 mitigates synucleinopathy.Cell death & disease · 2024Article
- A topographical atlas of α-synuclein dosage and cell type-specific expression in adult mouse brain and peripheral organs.NPJ Parkinson's disease · 2024Article
- RNA sequestration driven by amyloid formation: the alpha synuclein case.Nucleic acids research · 2023Article
- Unraveling the Complex Interplay between Alpha-Synuclein and Epigenetic Modification.International journal of molecular sciences · 2023Review
- Defining Specific Cell States of MPTP-Induced Parkinson's Disease by Single-Nucleus RNA Sequencing.International journal of molecular sciences · 2022Article
- Article
- CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates synaptic dysregulation in huntington's disease.Acta neuropathologica communications · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A growing body of evidence suggests that nuclear alpha-synuclein (αSyn) plays a role in the pathogenesis of Parkinson's disease (PD). However, this question has been difficult to address as controlling the localization of αSyn in experimental systems often requires protein overexpression, which affects its aggregation propensity. To overcome this, we engineered SncaNLS mice, which localize endogenous αSyn to the nucleus. We characterized these mice on a behavioral, histological and biochemical level to determine whether the increase of nuclear αSyn is sufficient to elicit PD-like phenotypes. SncaNLS mice exhibit age-dependent motor deficits and altered gastrointestinal function. We found that these phenotypes were not linked to αSyn aggregation or phosphorylation. Through histological analyses, we observed motor cortex atrophy in the absence of midbrain dopaminergic neurodegeneration. We sampled cortical proteomes of SncaNLS mice and controls to determine the molecular underpinnings of these pathologies. Interestingly, we found several dysregulated proteins involved in dopaminergic signaling, including Darpp32, Pde10a and Gng7, which we further confirmed was decreased in cortical samples of the SncaNLS mice compared with controls. These results suggest that chronic endogenous nuclear αSyn can elicit toxic phenotypes in mice, independent of its aggregation. This model raises key questions related to the mechanism of αSyn toxicity in PD and provides a new model to study an underappreciated aspect of PD pathogenesis.
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.