ArticleLife science alliance2024
c-KIT inhibitors reduce pathology and improve behavior in the Tg(SwDI) model of Alzheimer's disease.
Article in Life science alliance, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Discovering non-linear dynamics of miRNAs in Alzheimer's disease-related cognitive impairment: a cross-species approach with explainable machine learning.Biology direct · 2026Article
- Synergistic Effects of Multi-Kinase Inhibition onBiomedicines · 2026Article
- [Causal relationship between circulating cytokines and keloids: A Mendelian randomized study].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Modulation of Peripheral Mast Cell and Brain Microglia Axis via Kinase Inhibition.Metabolites · 2025Article
- TMF Attenuates Cognitive Impairment and Neuroinflammation by Inhibiting the MAPK/NF-κB Pathway in Alzheimer's Disease: A Multi-Omics Analysis.Marine drugs · 2025Article
- Mechanistic exploration of obesity-related indicators and motor cognitive risk syndrome: a mediated effect based on C-reactive protein triglyceride glucose index.Frontiers in aging neuroscience · 2025Article
- Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.Frontiers in dementia · 2024Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Treatments for Alzheimer's disease have primarily focused on removing brain amyloid plaques to improve cognitive outcomes in patients. We developed small compounds, known as BK40143 and BK40197, and we hypothesize that these drugs alleviate microglial-mediated neuroinflammation and induce autophagic clearance of neurotoxic proteins to improve behavior in models of neurodegeneration. Specificity binding assays of BK40143 and BK40197 showed primary binding to c-KIT/Platelet Derived Growth Factor Receptors (PDGFR)α/β, whereas BK40197 also differentially binds to FYVE finger-containing phosphoinositide kinase (PIKFYVE). Both compounds penetrate the CNS, and treatment with these drugs inhibited the maturation of peripheral mast cells in transgenic mice, correlating with cognitive improvements on measures of memory and anxiety. In the brain, microglial activation was profoundly attenuated and amyloid-beta and tau were reduced via autophagy. Multi-kinase inhibition, including c-KIT, exerts multifunctional effects to reduce neurodegenerative pathology via autophagy and microglial activity and may represent a potential therapeutic option for neurodegeneration.
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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.