ArticleEBioMedicine2019
Small molecule modulator of aggrephagy regulates neuroinflammation to curb pathogenesis of neurodegeneration.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Multi-Network Co-expression Analysis Enhances Biological Insights from Single-Cell Gene Expression.Interdisciplinary sciences, computational life sciences · 2026Article
- Tim-3 Deficiency Ameliorates Motor Deficits and Neuroinflammation in MPP+/MPTP-Induced Parkinson's Disease Models via the NF-κB/NLRP3 Pathway.Molecular neurobiology · 2025Article
- Strategies in Parkinson's Disease Therapeutics - A Need for Synergy of Ayurveda, Small Molecules and Nanoparticles aided Approaches.Current topics in medicinal chemistry · 2025Review
- An update on novel and emerging therapeutic targets in Parkinson's disease.Metabolic brain disease · 2024Review
- Neuroprotective Activity of a Non-Covalent Imatinib+TP10 Conjugate in HT-22 Neuronal Cells In Vitro.Pharmaceutics · 2024Article
- Single-cell aggrephagy-related patterns facilitate tumor microenvironment intercellular communication, influencing osteosarcoma progression and prognosis.Apoptosis : an international journal on programmed cell death · 2024Article
- What Can Inflammation Tell Us about Therapeutic Strategies for Parkinson's Disease?International journal of molecular sciences · 2024Review
- Molecular Modulators and Receptors of Selective Autophagy: Disease Implication and Identification Strategies.International journal of biological sciences · 2024Review
- Profiling tyrosine kinase inhibitors as AD therapeutics in a mouse model of AD.Molecular brain · 2023Article
- Review
- Article
- Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Bi-Directional Relationship Between Autophagy and Inflammasomes in Neurodegenerative Disorders.Cellular and molecular neurobiology · 2023Review
- Molecular and Cellular Interactions in Pathogenesis of Sporadic Parkinson Disease.International journal of molecular sciences · 2022Review
- Role of Ubiquitin-Proteasome and Autophagy-Lysosome Pathways in α-Synuclein Aggregate Clearance.Molecular neurobiology · 2022Review
- Roles for c-Abl in postoperative neurodegeneration.International journal of medical sciences · 2022Review
- Differences in Neuronal Numbers, Morphology, and Developmental Apoptosis in Mice Nigra Provide Experimental Evidence of Ontogenic Origin of Vulnerability to Parkinson's Disease.Neurotoxicity research · 2021Article
- Targeting autophagy using small-molecule compounds to improve potential therapy of Parkinson's disease.Acta pharmaceutica Sinica. B · 2021Review
- Selective autophagy as a therapeutic target for neurological diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson's Disease.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundPlethora of efforts fails to yield a single drug to reverse the pathogenesis of Parkinson's disease (PD) and related α-synucleopathies.
methodsUsing chemical biology, we identified a small molecule inhibitor of c-abl kinase, PD180970 that could potentially clear the toxic protein aggregates. Genetic, molecular, cell biological and immunological assays were performed to understand the mechanism of action. In vivo preclinical disease model of PD was used to assess its neuroprotection efficacy.
findingsIn this report, we show the ability of a small molecule inhibitor of tyrosine kinases, PD180970, to induce autophagy (cell lines and mice midbrain) in an mTOR-independent manner and ameliorate the α-synuclein mediated toxicity. PD180970 also exerts anti-neuroinflammatory potential by inhibiting the release of proinflammatory cytokines such as IL-6 (interleukin-6) and MCP-1 (monocyte chemoattractant protein-1) through reduction of TLR-4 (toll like receptor-4) mediated NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation. In vivo studies show that PD180970 is neuroprotective by degrading the toxic protein oligomers through induction of autophagy and subsiding the microglial activation.
interpretationThese protective mechanisms ensure the negation of Parkinson's disease related motor impairments. FUND: This work was supported by Wellcome Trust/DBT India Alliance Intermediate Fellowship (500159-Z-09-Z), DST-SERB grant (EMR/2015/001946), DBT (BT/INF/22/SP27679/2018) and JNCASR intramural funds to RM, and SERB, DST (SR/SO/HS/0121/2012) to PAA, and DST-SERB (SB/YS/LS-215/2013) to JPC and BIRAC funding to ETA C-CAMP.
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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.