- |||||||||| Zyclara (imiquimod) / Mochida, Mylan, Bausch Health, Vesimune (imiquimod) / UroGen
Preclinical, Journal: IL-33 contributes to disease severity in Psoriasis-like models of mouse. (Pubmed Central) - Aug 7, 2020 Thus, IL-33 appears to be a major risk factor for severity of psoriasis-like skin inflammation. Our findings may open new perspectives for understanding the mechanisms and developing a therapeutic strategy for psoriasis.
- |||||||||| selisistat (SEN-196) / AOP Orphan Pharma
Journal: 4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages. (Pubmed Central) - Aug 7, 2020 Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expres- sion of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of T. gondii parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1- mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.
- |||||||||| sirolimus / Generic mfg.
Journal: Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: implications for Parkinson disease. (Pubmed Central) - Aug 6, 2020 Thus, we demonstrated that Ka promotes neuroinflammatory inhibition via the cooperation of ubiquitination and autophagy, suggesting that Ka is a promising therapeutic strategy for the treatment of NDDs. Abbreviations: 3-MA: 3-methyladenine; AAV: adeno-associated virus; ACTB: actin, beta; AIF1/IBA1: allograft inflammatory factor 1; ATG5: autophagy related 5; ATG7: autophagy related 7; BafA1: bafilomycin A BECN1: beclin 1, autophagy related; CASP1: caspase 1; CNS: central nervous system; CQ: chloroquine; DA neurons: dopaminergic neurons; DAMPS: damage-associated molecular patterns; DAPI: 4',6-diamidino-2-phenylindole; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; GFAP: glial fibrillary acidic protein; IP: immunoprecipitation; i.p.: intraperitoneally; Ka: kaempferol; KD: knockdown; KO: knockout; LPS: lipopolysaccharide; IL1B: interleukin 1 beta; IL6: interleukin 6; Ly: lysate; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NC: negative control; NDD: neurodegenerative diseases; NLRP3: NLR family, pyrin domain containing 3; OE: overexpression; PD: Parkinson disease; poly-Ub: poly-ubiquitin; PTM: post-translational modification; PYCARD/ASC: PYD and CARD domain containing; Rapa: rapamycin; RFP: red fluorescent protein; SN: supernatant; SNCA: synuclein alpha; SNpc: substantia nigra pars compacta; SQSTM1: sequestosome 1; TH: tyrosine hydroxylase; TNF/TNF-alpha: tumor necrosis factor; Ub: ubiquitin; WT: wild type.
- |||||||||| Journal: HHV-6B reduces autophagy and induces ER stress in primary monocytes impairing their survival and differentiation into dendritic cells. (Pubmed Central) - Aug 5, 2020
In agreement with the previous finding that HHV-6B dysregulated autophagy and induced endoplasmic reticulum (ER) stress in cells in which it replicated, here we found that these effects occurred also in differentiating monocytes and that ER stress relief, by using the chemical chaperone sodium 4-phenylbutirate (PBA), partially restored DC formation. This suggests that the induction of ER stress, likely exacerbated by autophagy inhibition, could contribute to the immune suppression induced by HHV-6B derived from exanthema subitem patients.
- |||||||||| Journal: Human papillomavirus 16E6/E7 activates autophagy via Atg9B and LAMP1 in cervical cancer cells. (Pubmed Central) - Aug 4, 2020
These compounds represent not only a new resource for the study of autophagy but also potential chemical starting points for the validation or invalidation of these two centrally important autophagy kinases in disease models. Our findings verified that 16E6/E7 activated autophagy via accelerating autophagosome formation and degradation, and Atg9B and LAMP1 were involved in the process of 16E6/E7 modulating autophagy, suggesting that targeting autophagy may be a potential approach in cervical cancer therapeutics.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: ERβ promotes Aβ degradation via the modulation of autophagy. (Pubmed Central) - Aug 4, 2020 Aβ or CQ induced cytotoxicity was restored by a selective ERβ activator diarylpropionitrile (DPN). Collectively, these data indicate that overexpression of ERβ exerts a neuroprotective effect through interacting with ATG7 protein and further enhances autophagy-lysosomal activity for Aβ clearance at the cellular level.
- |||||||||| Preclinical, Journal: Homocysteine enhances neural stem cell autophagy in in vivo and in vitro model of ischemic stroke. (Pubmed Central) - Aug 4, 2020
In addition, MHY1485, an activator of mTOR, reduced Hcy-induced increase in LC3 and Beclin 1 protein levels, meanwhile ERK and PI3K activators (TPA, curcumin for ERK and IGF-1 for PI3K, respectively) enhanced Hcy-triggered mTOR inhibition in OGD/R NSCs. Our findings suggest that Hcy may cause excessive autophagy by downregulation of both PI3K-AKT- and ERK- dependent mTOR signaling, thereby facilitates the toxicity of Hcy on NSCs in ischemic brains.
- |||||||||| hydroxychloroquine / Generic mfg.
Review, Journal: Targeting Autophagy in Cancer: Recent Advances and Future Directions. (Pubmed Central) - Aug 4, 2020 We also highlight clinical efforts to repurpose lysosomal inhibitors, such as hydroxychloroquine, as anticancer agents that block autophagy, as well as the development of more potent and specific autophagy inhibitors for cancer treatment, and review future directions for autophagy research...A deeper understanding of autophagy within the tumor microenvironment has enabled the development of novel inhibitors and clinical trial strategies. Challenges and opportunities remain to identify patients most likely to benefit from this approach.
- |||||||||| Journal: iNOS Interacts with Autophagy Receptor p62 and is Degraded by Autophagy in Macrophages. (Pubmed Central) - Aug 4, 2020
Finally, we showed that autophagy negatively regulated the generation of NO in macrophages, which is consistent with the changes of iNOS levels. Collectively, our study revealed a previously unknown mechanism by which autophagy regulates iNOS levels to modulate NO production during inflammation.
- |||||||||| Journal: Degradable Nanoparticles Restore Lysosomal pH and Autophagic Flux in Lipotoxic Pancreatic Beta Cells. (Pubmed Central) - Aug 2, 2020
PLGA NPs display a concentration dependent performance with higher concentrations of PLGA NPs, lowering lysosomal pH, as well as restoring autophagic flux and insulin secretion in pancreatic β-cells. These results document that acidifying the lysosome, via an external perturbation, in lipotoxic pancreatic β-cells affords a specific biological outcome of improved cellular degradative activity.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: The role of autophagy in the pathogenesis of exposure keratitis. (Pubmed Central) - Aug 2, 2020 Each of these models was treated with either an autophagy inhibitor [chloroquine (CQ) or 3-methyladenine (3-MA)] or activator [Rapamycin (Rapa)]...Furthermore, the phosphorylation status of PERK and eIF2α and CHOP expression increased in both EK models indicating that ER stress-induced autophagy promoted cell survival. Taken together, air exposure-induced autophagy is indispensable for the maintenance of corneal epithelial physiology and cell survival.
- |||||||||| tamoxifen / Generic mfg.
Journal: The long noncoding RNA H19 promotes tamoxifen resistance in breast cancer via autophagy. (Pubmed Central) - Aug 2, 2020 These findings provide potential therapeutic strategies that target autophagy to limit the pathogenesis and progression of BC. Our findings demonstrate that H19 induces autophagy activation via the H19/SAHH/DNMT3B axis, which could contribute to tamoxifen resistance in breast cancer.
- |||||||||| MK-2206 / Merck (MSD), hydroxychloroquine / Generic mfg., cisplatin / Generic mfg.
Journal: Paeonol induces cytoprotective autophagy via blocking the Akt/mTOR pathway in ovarian cancer cells. (Pubmed Central) - Aug 2, 2020 Taken together, our results demonstrate that Pae induced cytoprotective autophagy by inhibiting the Akt/mTOR pathway in ovarian cancer cells. Thus, the strategy of combining Pae with an autophagy inhibitor to block Akt/mTOR-dependent autophagy could enhance the antitumour activity of Pae and warrants further application for the treatment of ovarian cancer.
- |||||||||| fluorouracil / Generic mfg., Tagrisso (osimertinib) / AstraZeneca
Journal: MCT1 relieves osimertinib-induced CRC suppression by promoting autophagy through the LKB1/AMPK signaling. (Pubmed Central) - Aug 2, 2020 Notably, OSI significantly exaggerates the sensitivity of CRC cells to the first-line drugs 5-fluorouracil or oxaliplatin. Taken together, our study unravels a novel mechanism of OSI-mediated protective autophagy involving MCT1/LKB1/AMPK signaling, and suggests the use of OSI as a potential agent for clinical CRC treatment.
- |||||||||| sirolimus / Generic mfg.
Journal: The role of the LncRNA-FA2H-2-MLKL pathway in atherosclerosis by regulation of autophagy flux and inflammation through mTOR-dependent signaling. (Pubmed Central) - Jul 31, 2020 In vivo experiments with apoE knockout mice fed a western diet demonstrated that LncRNA-FA2H-2 knockdown decreased microtubule-associated expression of microtubule-associated protein 1 light chain 3 II and lysosome-associated membrane protein 1, but increased expression of sequestosome 1 (p62), MLKL, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and interleukin-6 in atherosclerotic lesions. Our findings indicated that the lncRNA-FA2H-2-MLKL pathway is essential for regulation of autophagy and inflammation, and suggested that lncRNA-FA2H-2 and MLKL could act as potential therapeutic targets to ameliorate atherosclerosis-related diseases.
- |||||||||| Journal: SIRT6 promotes the EMT of hepatocellular carcinoma by stimulating autophagic degradation of E-cadherin. (Pubmed Central) - Jul 31, 2020
These results established a relationship between SIRT6 and HCC EMT and further elucidated the mechanisms underlying HCC metastasis, helping provide a promising approach for the treatment of HCC. Implications: Inhibiting SIRT6 represents a potential therapeutic approach to suppress HCC metastasis partially through reduction of autophagic degradation of E-cadherin.
- |||||||||| hydroxychloroquine / Generic mfg.
Journal: The role of autophagy in HER2-targeted therapy. (Pubmed Central) - Jul 31, 2020 Since the autophagy inhibitors chloroquine and hydroxychloroquine are approved drugs for the treatment of malaria, autophagy inhibition is discussed as an option to enhance the effect of certain anticancer treatments or to overcome resistance against cancer therapies. In this review we focus on autophagy and its role in the response to HER2-targeted therapies for breast and gastrointestinal tumours.
- |||||||||| Review, Journal: The role of autophagy in resistance to targeted therapies. (Pubmed Central) - Jul 30, 2020
Here, we summarize recent studies that investigated the role of autophagy in drug resistance after targeted therapy in different types of cancers. We highlight positive results and limitations of pre-clinical and clinical studies in which autophagy inhibitors are used in combination with targeted therapies.
- |||||||||| chloroquine phosphate / Generic mfg.
Preclinical, Journal: Inhibition of autophagy alleviates cadmium-induced mouse spleen and human B cells apoptosis. (Pubmed Central) - Jul 29, 2020 Taken together, these results indicate Cd induced autophagy, promotes apoptosis in immune cells, and inhibition of autophagy can alleviate Cd induced spleen and immune cell apoptosis. This study might provide the groundwork for future studies on Cd induced immunomodulatory effects and immune diseases.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Arctigenin suppresses cell proliferation via autophagy inhibition in hepatocellular carcinoma cells. (Pubmed Central) - Jul 29, 2020 The stage of inhibition in autophagy by ARG differed from those by the autophagy inhibitors 3-methyladenine (3-MA) or chloroquine (CQ)...Further analysis of apoptosis-related proteins indicated that ARG did not affect caspase-3 activation and PARP cleavage, suggesting that the antiproliferative effect of ARG can occur independently of apoptosis. In summary, our study showed that ARG suppresses cell proliferation and inhibits autophagy, and might lead to the development of agents for autophagy research and cancer chemoprevention.
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