ArticleAutophagy2013
Tyrosine kinase inhibition facilitates autophagic SNCA/α-synuclein clearance.
Article in Autophagy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02921477 (Open Label Study for the Use of Tyrosine Kinase Inhibitors for Treatment of Cognitive Decline Due to Degenerative Dementias), which is not on this map. Cited by 37 papers.
What it found
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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.
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.
Open Label Study for the Use of Tyrosine Kinase Inhibitors for Treatment of Cognitive Decline Due to Degenerative Dementias
Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Decoding unchanged transcriptome of Alzheimer's disease reveals an NCAM1 mRNA switch as a potential biomarker.iScience · 2026Article
- Investigation of neuroprotective and antiapoptotic effects of rosmarinic acid in anIranian journal of basic medical sciences · 2026Article
- c-Abl Inhibitors in Parkinson's: Exploring Hypotheses on Alpha-Synuclein Modulation.Advanced pharmaceutical bulletin · 2025Article
- c-KIT inhibitors reduce pathology and improve behavior in the Tg(SwDI) model of Alzheimer's disease.Life science alliance · 2024Article
- Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.Frontiers in dementia · 2024Review
- Lewy Body Dementia: An Overview of Promising Therapeutics.Current neurology and neuroscience reports · 2023Review
- Inhibition of discoidin domain receptor (DDR)-1 with nilotinib alters CSF miRNAs and is associated with reduced inflammation and vascular fibrosis in Alzheimer's disease.Journal of neuroinflammation · 2023Article
- Functional and Pathological Effects of α-Synuclein on Synaptic SNARE Complexes.Journal of molecular biology · 2023Review
- Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington's Disease Patients.Metabolites · 2022Article
- Inhibition of Ubiquitin-Specific Protease-13 Improves Behavioral Performance in Alpha-Synuclein Expressing Mice.International journal of molecular sciences · 2022Article
- Association of p53 with Neurodegeneration in Parkinson's Disease.Parkinson's disease · 2022Review
- CSF MicroRNAs Reveal Impairment of Angiogenesis and Autophagy in Parkinson Disease.Neurology. Genetics · 2021Article
- Nilotinib Improves Bioenergetic Profiling in Brain Astroglia in the 3xTg Mouse Model of Alzheimer's Disease.Aging and disease · 2021Article
- α-Synucleinopathy associated c-Abl activation causes p53-dependent autophagy impairment.Molecular neurodegeneration · 2020Article
- Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Review
- Multikinase Abl/DDR/Src Inhibition Produces Optimal Effects for Tyrosine Kinase Inhibition in Neurodegeneration.Drugs in R&D · 2019Article
- Nilotinib-Induced Dystonia and Cognitive Deficits in a Neurologically Normal Patient with Chronic Myeloid Leukemia.Case reports in neurological medicine · 2019Article
- Author's Reply to Segura-Aguilar: Autophagosome maturation not autophagy induction is impaired in neurodegeneration.CNS drugs · 2018Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The effects of ABL1/ABL inhibition on clearance of SNCA/α-synuclein were evaluated in animal models of α-synucleinopathies. Parkinson disease (PD) is a movement disorder characterized by death of dopaminergic substantia nigra (SN) neurons and brain accumulation of SNCA. The tyrosine kinase ABL1 is activated in several neurodegenerative diseases. An increase in ABL1 activity is detected in human postmortem PD brains. Lentiviral expression of SNCA in the mouse SN activates ABL1 via phosphorylation, while lentiviral Abl expression increases SNCA levels. Administration of the brain-penetrant tyrosine kinase inhibitor Nilotinib decreases Abl activity and facilitates autophagic clearance of SNCA in transgenic and lentiviral gene transfer models. Subcellular fractionation demonstrates accumulation of SNCA and hyperphosphorylated MAPT/Tau (p-MAPT) in autophagic vacuoles in SNCA-expressing brains, while Nilotinib treatment leads to protein deposition into the lysosomes, suggesting enhanced autophagic clearance. These data suggest that Nilotinib may be a therapeutic strategy to degrade SNCA in PD and other α-synucleinopathies.
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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.