ArticleThe Journal of clinical investigation2016
Activation of tyrosine kinase c-Abl contributes to α-synuclein-induced neurodegeneration.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 205 citations in OpenAlex.
- Nilotinib in Parkinson's disease: A systematic review and meta-analysis.Frontiers in aging neuroscience · 2022Pooled 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
- A Phase I, Randomized, SAD, MAD, and PK Study of Risvodetinib in Older Adults and Parkinson's Disease.Journal of Parkinson's disease · 2024Trial
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- The emerging role and therapeutic targeting of autophagy-lysosome pathway in the pathogenesis of Parkinson's disease.Translational neurodegeneration · 2026Review
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Drug repurposing for disease-modifying effects in multiple system atrophy.Translational neurodegeneration · 2026Review
- Evaluation of c-Abl inhibitor vodobatinib in subjects with early Parkinson's disease: a phase 2, randomized, double-blind, placebo-controlled study.NPJ Parkinson's disease · 2026Article
- Investigation of neuroprotective and antiapoptotic effects of rosmarinic acid in anIranian journal of basic medical sciences · 2026Article
- Alpha-Synuclein Neurobiology in Parkinson's Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspectives.Brain sciences · 2025Review
- Genetic code expansion and enzymatic modifications as accessible methods for studying site-specific post-translational modifications of alpha-synuclein and tau.Protein science : a publication of the Protein Society · 2025Article
- Infection and herbicide exposure implicate c-Abl kinase in α-Synuclein Ser129 phosphorylation.Cell communication and signaling : CCS · 2025Article
- Lewy body dementia promotion by air pollutants.Science (New York, N.Y.) · 2025Article
- Nonreceptor tyrosine kinase ABL1 regulates lysosomal acidification by phosphorylating the ATP6V1B2 subunit of the vacuolar-type HAutophagy · 2025Article
- Molecular mechanisms and consequences of TDP-43 phosphorylation in neurodegeneration.Molecular neurodegeneration · 2025Review
- Neuroprotective and Anti-Inflammatory Activity ofMarine drugs · 2025Article
- Article
- Drug Repositioning and Repurposing for Disease-Modifying Effects in Parkinson's Disease.Journal of movement disorders · 2025Article
- c-Abl Inhibitors in Parkinson's: Exploring Hypotheses on Alpha-Synuclein Modulation.Advanced pharmaceutical bulletin · 2025Article
- Preclinical studies and transcriptome analysis in a model of Parkinson's disease with dopaminergic ZNF746 expression.Molecular neurodegeneration · 2025Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 4 countries.
Funding
Abstract
Aggregation of α-synuclein contributes to the formation of Lewy bodies and neurites, the pathologic hallmarks of Parkinson disease (PD) and α-synucleinopathies. Although a number of human mutations have been identified in familial PD, the mechanisms that promote α-synuclein accumulation and toxicity are poorly understood. Here, we report that hyperactivity of the nonreceptor tyrosine kinase c-Abl critically regulates α-synuclein-induced neuropathology. In mice expressing a human α-synucleinopathy-associated mutation (hA53Tα-syn mice), deletion of the gene encoding c-Abl reduced α-synuclein aggregation, neuropathology, and neurobehavioral deficits. Conversely, overexpression of constitutively active c-Abl in hA53Tα-syn mice accelerated α-synuclein aggregation, neuropathology, and neurobehavioral deficits. Moreover, c-Abl activation led to an age-dependent increase in phosphotyrosine 39 α-synuclein. In human postmortem samples, there was an accumulation of phosphotyrosine 39 α-synuclein in brain tissues and Lewy bodies of PD patients compared with age-matched controls. Furthermore, in vitro studies show that c-Abl phosphorylation of α-synuclein at tyrosine 39 enhances α-synuclein aggregation. Taken together, this work establishes a critical role for c-Abl in α-synuclein-induced neurodegeneration and demonstrates that selective inhibition of c-Abl may be neuroprotective. This study further indicates that phosphotyrosine 39 α-synuclein is a potential disease indicator for PD and related α-synucleinopathies.
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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.