ArticleCNS neuroscience & therapeutics2019
Rapamycin and FK506 derivative TH2849 could ameliorate neurodegenerative diseases through autophagy with low immunosuppressive effect.
Article in CNS neuroscience & therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Rapamycin and Autophagy: Potential Therapeutic Approach for Parkinson's Disease Treatment.CNS & neurological disorders drug targets · 2026Review
- mTOR signaling and Alzheimer's disease: What we know and where we are?CNS neuroscience & therapeutics · 2024Review
- Melatonin inhibits Japanese encephalitis virus replication and neurotoxicity via calcineurin-autophagy pathways.BMC neuroscience · 2023Article
- Zebrafish as a Model Organism for Studying Pathologic Mechanisms of Neurodegenerative Diseases and other Neural Disorders.Cellular and molecular neurobiology · 2023Review
- Neurodegeneration, Mitochondria, and Antibiotics.Metabolites · 2023Review
- Autophagy Modulation in Aggresome Formation: Emerging Implications and Treatments of Alzheimer's Disease.Biomedicines · 2022Review
- Intelligent lesion blood-brain barrier targeting nano-missiles for Alzheimer's disease treatment by anti-neuroinflammation and neuroprotection.Acta pharmaceutica Sinica. B · 2022Article
- Autophagy-targeted therapy to modulate age-related diseases: Success, pitfalls, and new directions.Current research in pharmacology and drug discovery · 2021Review
- Effects of autophagy inducers on recombinant antibody production in insect cells.Cytotechnology · 2020Article
- Rapamycin and FK506 derivative TH2849 could ameliorate neurodegenerative diseases through autophagy with low immunosuppressive effect.CNS neuroscience & therapeutics · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is an essential cellular process concern with cellular homeostasis down-regulated by mTOR, whose activity can be modulated by rapamycin, a kind of lipophilic macrolide antibiotic, through forming a complex with immunophilin FKBP12 essential for mTOR regulation to induce autophagy. Therefore, rapamycin is normally used as a neuron protective agent. The immunophilin FKBP12 binding ligand FK506 is well known as an immunosuppressive agent by inhibiting the calcineurin expression. In this study, we synthesized a series of modified compounds based on the FKBP12 binding moiety to as same as the binding structure of rapamycin and FK506 particularly. We removed the other binding regions of the complex that has the property of immunosuppression. We found that a novel small molecule named TH2849 from these derivative compounds has a significant binding connection with mTOR by comparing to calcineurin. The effects of TH2849 on calcineurin/NFAT were not as significant as FK506, and weak effects on IL2/p34
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