ArticleNature neuroscience2013
Parthanatos mediates AIMP2-activated age-dependent dopaminergic neuronal loss.
Article in Nature neuroscience, 2013. 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 137 papers, 1 of them a synthesis that pooled it.
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
137 citing papers in PubMed, 1 synthesis or guideline pooled it, 214 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- The 201 Trial: a placebo-controlled randomized phase 2 study of safety and tolerance of the c-Abl kinase inhibitor risvodetinib in untreated Parkinson's disease.Nature aging · 2026Trial
- Metabolic hallmarks of regulated cell death.Cell research · 2026Review
- Computational Evaluation of Potential c-Abl Kinase Inhibitors for Parkinson's Disease: QSAR, Docking, Bioisosteric Replacement, ADMET, and MD Simulations.Applied biochemistry and biotechnology · 2025Article
- Moyamoya Disease and the Risk of Parkinson's Disease.Annals of clinical and translational neurology · 2025Article
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- Aging, cellular senescence and Parkinson's disease.Journal of Parkinson's disease · 2025Review
- Preclinical studies and transcriptome analysis in a model of Parkinson's disease with dopaminergic ZNF746 expression.Molecular neurodegeneration · 2025Article
- Targeting the PARylation-Dependent Ubiquitination Signaling Pathway for Cancer Therapies.Biomolecules · 2025Review
- Compensatory synaptotagmin-11 expression conceals parkinson's disease-like phenotypes in parkin knockout mice.Cell communication and signaling : CCS · 2025Article
- Neuronal LAG3 facilitates pathogenic α-synuclein neuron-to-neuron propagation.bioRxiv : the preprint server for biology · 2025Article
- The Dual Role of Survival Genes in Neurons and Cancer Cells: a Strategic Clinical Application of DX2 in Neurodegenerative Diseases and Cancer.Biomolecules & therapeutics · 2025Review
- α-Synuclein pathology as a target in neurodegenerative diseases.Nature reviews. Neurology · 2025Review
- AIMP2 accumulation in brain leads to cognitive deficits and blood secretion in Parkinson's disease.Journal of translational medicine · 2024Article
- Parthanatos: Mechanisms, modulation, and therapeutic prospects in neurodegenerative disease and stroke.Biochemical pharmacology · 2024Review
- Neuroprotective Activity of a Non-Covalent Imatinib+TP10 Conjugate in HT-22 Neuronal Cells In Vitro.Pharmaceutics · 2024Article
- Brain-targeted delivery of neuroprotective survival gene minimizing hematopoietic cell contamination: implications for Parkinson's disease treatment.Journal of translational medicine · 2024Article
- Bi-directional regulation of AIMP2 and its splice variant on PARP-1-dependent neuronal cell death; Therapeutic implication for Parkinson's disease.Acta neuropathologica communications · 2024Article
- Revisiting the potential of regulated cell death in glioma treatment: a focus on autophagy-dependent cell death, anoikis, ferroptosis, cuproptosis, pyroptosis, immunogenic cell death, and the crosstalk between them.Frontiers in oncology · 2024Review
- Nicotinamide Adenine Dinucleotide (NADAntioxidants & redox signaling · 2023Review
77 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The defining pathogenic feature of Parkinson's disease is the age-dependent loss of dopaminergic neurons. Mutations and inactivation of parkin, an ubiquitin E3 ligase, induce Parkinson's disease through accumulation of pathogenic substrates. We found that transgenic overexpression of a parkin substrate, aminoacyl-tRNA synthetase complex interacting multifunctional protein-2 (AIMP2), led to a selective, age-dependent, progressive loss of dopaminergic neurons via activation of poly(ADP-ribose) polymerase-1 (PARP1). AIMP2 accumulation in vitro and in vivo resulted in PARP1 overactivation and dopaminergic cell toxicity via direct association of these proteins in the nucleus, providing a path to PARP1 activation other than DNA damage. Inhibition of PARP1 through gene deletion or drug inhibition reversed behavioral deficits and protected against dopamine neuron death in AIMP2 transgenic mice. These data indicate that brain-permeable PARP inhibitors could effectively delay or prevent disease progression in Parkinson's disease.
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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.