更新于：2024-11-01

自噬蛋白

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与自噬蛋白相关的药物

LT-4008

靶点

自噬蛋白

作用机制

Autophagy protein inhibitors

在研机构

LTT Bio-Pharma Co., Ltd.

原研机构

LTT Bio-Pharma Co., Ltd.

在研适应症

血液肿瘤

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

LT-4007

靶点

自噬蛋白

作用机制

Autophagy protein stimulators

在研机构

LTT Bio-Pharma Co., Ltd.

原研机构

LTT Bio-Pharma Co., Ltd.

在研适应症

神经变性

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

TheraPBC(Theranostec)

靶点

自噬蛋白

作用机制

Autophagy protein inhibitors

在研机构

Theranostec Inc

原研机构

Theranostec Inc

在研适应症

膀胱癌 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与自噬蛋白相关的临床结果

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100 项与自噬蛋白相关的转化医学

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0 项与自噬蛋白相关的专利（医药）

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项与自噬蛋白相关的文献（医药）

2024-09-01·International Immunopharmacology

Protective effects and regulatory mechanisms of Platycodin D against LPS-Induced inflammatory injury in BEAS-2B cells

Article

作者: Cao, Yuxin ; Zhang, Yanqing ; Zhao, Xiaotong ; Xie, Junbo ; Li, Wei

Platycodin D (PLD), a major bioactive component of triterpene saponins found in Platycodon grandiflora, is renowned for its anti-inflammatory and antioxidant properties. This study aims to explore the protective effects and regulatory mechanisms of PLD in an LPS-induced inflammation injury model of BEAS-2B cells. Initially, PLD was identified from Platycodon grandiflora extracts utilizing UPLC-Q-TOF-MS/MS technology. The effects of PLD on the viability, morphology, ROS levels, and inflammatory factors of LPS-induced BEAS-2B cells were then investigated. The results showed that PLD significantly alleviated LPS-induced oxidative stress and inflammatory injury. Further analysis revealed that PLD positively influenced apoptosis levels, mitochondrial morphology, and related gene expression, indicating its potential to mitigate LPS-induced apoptosis and alleviate mitochondrial dysfunction. Using molecular docking technology, we predicted the binding sites of PLD with mitochondrial autophagy protein. Gene expression levels of autophagy-related proteins were measured to determine the impact of PLD on mitochondrial autophagy. Additionally, the study examined whether the mitochondrial autophagy agonists rapamycin (RAPA) could modulate the upregulation of inflammasome-related factors NLRP3 and Caspase-1 in LPS-induced BEAS-2B cells. This was done to evaluate the regulator mechanisms of PLD in pulmonary inflammatory injury. Our findings suggest that PLD's mechanism of action involves the regulation of mitochondrial autophagy, which in turn modulates inflammatory responses.

2024-06-01·International Journal of Immunogenetics

Impact of IRGM gene promoter polymorphisms on susceptibility to chronic HBV infection

Article

作者: Ouyang, Yaoling ; Cheng, Hai ; Li, Chengbin

AbstractThe autophagy gene immunity‐related GTPase M (IRGM) can affect the immune response against intracellular pathogens. The study was performed to determine any possible association between three IRGM single‐nucleotide polymorphisms (SNPs) (rs4958842, rs4958843 and rs4958846) and chronic hepatitis B virus (HBV) infection. A total of 171 chronic HBV‐infected individuals and 171 healthy controls were collected. Peripheral blood cells and Sanger sequencing were used to extract genomic DNA and determine the SNP genotypes, respectively. The C allele of rs4958843 is a risk factor for chronic HBV infection in various genetic models, including allelic, codominant and dominant models, with the following respective statistical data: allelic (T vs. C: OR = 1.371, 95% CI = 1.009–1.863, p = .043), codominant (TT vs. CC: OR = 2.137, 95% CI = 1.104–4.138, p = .024) and dominant (TT + TC vs. CC: OR = 1.976, 95% CI = 1.106–3.533, p = .021) models. The genotype and allele distributions of rs4958842 and rs4958846 showed no significant differences between chronic HBV infection patients and healthy controls. IRGM rs4958843 CC genotype carriers had significantly elevated values of alanine transaminase, aspartate transaminase alpha‐fetoprotein and total bilirubin (OR = 3.467, 95%CI = 1.167–10.298), which was positively associated with the disease progression of HBV infection. Mutant allele C of IRGM rs4958843 polymorphism is associated with the risk of chronic HBV infection in the Han people in central China and contributes to the disease progression.

2024-01-01·Theranostics

Lens autophagy protein ATG16L1: a potential target for cataract treatment

Article

作者: Yao, Ke ; Bao, Jing ; Yin, Qichuan ; Yu, Xiaoning ; Chen, Ruoqi ; Ping, Xiyuan ; Shi, Silu ; Chen, Xiangjun ; Yang, Hao ; Cui, Yilei ; Huang, Yuxin ; Shentu, Xingchao

Rationale: Cataract is the leading cause of blindness and low vision worldwide, yet its pathological mechanism is not fully understood. Although macroautophagy/autophagy is recognized as essential for lens homeostasis and has shown potential in alleviating cataracts, its precise mechanism remains unclear. Uncovering the molecular details of autophagy in the lens could provide targeted therapeutic interventions alongside surgery. Methods: We monitored autophagic activities in the lens and identified the key autophagy protein ATG16L1 by immunofluorescence staining, Western blotting, and transmission electron microscopy. The regulatory mechanism of ATG16L1 ubiquitination was analyzed by co-immunoprecipitation and Western blotting. We used the crystal structure of E3 ligase gigaxonin and conducted the docking screening of a chemical library. The effect of the identified compound riboflavin was tested in vitro in cells and in vivo animal models. Results: We used HLE cells and connexin 50 (cx50)-deficient cataract zebrafish model and confirmed that ATG16L1 was crucial for lens autophagy. Stabilizing ATG16L1 by attenuating its ubiquitination-dependent degradation could promote autophagy activity and relieve cataract phenotype in cx50-deficient zebrafish. Mechanistically, the interaction between E3 ligase gigaxonin and ATG16L1 was weakened during this process. Leveraging these mechanisms, we identified riboflavin, an E3 ubiquitin ligase-targeting drug, which suppressed ATG16L1 ubiquitination, promoted autophagy, and ultimately alleviated the cataract phenotype in autophagy-related models. Conclusions: Our study identified an unrecognized mechanism of cataractogenesis involving ATG16L1 ubiquitination in autophagy regulation, offering new insights for treating cataracts.