Autophagy, a crucial intracellular degradation process facilitated by lysosomes, plays a pivotal role in maintaining cellular homeostasis. The elucidation of autophagy key genes and signaling pathways has significantly advanced our understanding of this process and has led to the exploration of autophagy as a promising therapeutic approach. This review comprehensively assesses the latest developments in small molecule modulators targeting autophagy. Moreover, the review delves into the most recent strategies for drug discovery, specifically focusing on selective agents that exploit autophagosomes and lysosomes for targeted protein degradation. Additionally, this article highlights the prevailing challenges and outlines potential future advancements in the field. By amalgamating the cutting-edge knowledge in the field, we aim to offer valuable insights and references for the anti-cancer drug development of autophagy-targeted therapies, thus contributing to the advancement of novel therapeutic interventions.
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http://dx.doi.org/10.1016/j.ejmech.2024.116688 | DOI Listing |
Inflammation
December 2024
Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, Guangdong Province, China.
The main pathogenic mechanism of HIV-associated neurocognitive disorders (HAND) is neuronal apoptosis induced by inflammatory mediators, in which microglial inflammation plays a crucial role. However, the exact pathogenic mechanism remains unclear. Previous studies have shown that the HIV-1 gp120 V3 loop can trigger inflammation in CHME-5 microglia.
View Article and Find Full Text PDFVirulence
December 2025
Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Amino acid metabolism provides significant insight into the development and prevention of many viral diseases. Therefore, the present study aimed to compare the amino acid profiles of hand, foot, and mouth disease (HFMD) patients with those of healthy individuals and to further reveal the molecular mechanisms of HFMD severity. Using UPLC-MS/MS, we determined the plasma amino acid expression profiles of pediatric patients with HFMD (mild, = 42; severe, = 43) and healthy controls ( = 25).
View Article and Find Full Text PDFCancer Sci
December 2024
Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Patient-derived organoids represent a novel platform to recapitulate the cancer cells in the patient tissue. While cancer heterogeneity has been extensively studied by a number of omics approaches, little is known about the spatiotemporal kinase activity dynamics. Here we applied a live imaging approach to organoids derived from 10 pancreatic ductal adenocarcinoma (PDAC) patients to comprehensively understand their heterogeneous growth potential and drug responses.
View Article and Find Full Text PDFNeuro Oncol
December 2024
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Background: Selinexor is a selective inhibitor of exportin-1 (XPO1), a key mediator of the nucleocytoplasmic transport for molecules critical to tumor cell survival. Selinexor's lethality is generally associated with the induction of apoptosis, and in some cases, with autophagy-induced apoptosis. We performed this study to determine Selinexor's action in glioblastoma (GBM) cells, which are notoriously resistant to apoptosis.
View Article and Find Full Text PDFJ Transl Med
December 2024
Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
Background: Mitochondrial transcription elongation factor (TEFM) is a recently discovered factor involved in mitochondrial DNA replication and transcription. Previous studies have reported that abnormal TEFM expression can disrupt the assembly of mitochondrial respiratory chain and thus mitochondrial function. However, the role of TEFM on Uterine corpus endometrial carcinoma (UCEC) progression remains unclear.
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