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NOVEL APPROACHES IN TARGETING MEMBRANE AND SECRETED PROTEINS FOR LYSOSOMAL DEGRADATION.
Chembiochem
December 2024
Illinois State University, Chemistry, UNITED STATES OF AMERICA.
Protein degradation is pivotal for all biochemical aspects of cellular function. In mammalian cells, protein degradation is mediated mainly by the ubiquitin proteasome system (UPS) and the autophagic-lysosomal system (ALS). Over the last two decades, different types of targeted protein degradation approaches have been developed including proteolysis targeting chimeras (PROTACs) and lysosome targeting chimeras (LYTACs), which employ the UPS to degrade intracellular proteins and the ALS to degrade extracellular and membrane proteins respectively.
View Article and Find Full Text PDFBaicalein tethers CD274/PD-L1 for autophagic degradation to boost antitumor immunity.
Autophagy
December 2024
Institute of Energy Metabolism and Health, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Immune checkpoint inhibitors, especially those targeting CD274/PD-L1yield powerful clinical therapeutic efficacy. Thoughmuch progress has been made in the development of antibody-basedCD274 drugs, chemical compounds applied for CD274degradation remain largely unavailable. Herein,baicalein, a monomer of traditional Chinese medicine, isscreened and validated to target CD274 and induces itsmacroautophagic/autophagic degradation.
View Article and Find Full Text PDFCannabidiol induces autophagy via CB receptor and reduces α-synuclein cytosolic levels.
Brain Res
December 2024
Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
Numerous studies have explored the role of cannabinoids in neurological conditions, chronic pain and neurodegenerative diseases. Restoring autophagy has been proposed as a potential target for the treatment of neurodegenerative diseases. In our study, we used a neuroblastoma cell line that overexpresses wild-type α-synuclein to investigate the effects of cannabidiol on autophagy modulation and reduction in the level of cytosolic α-synuclein.
View Article and Find Full Text PDFThe N-degron pathway mediates the autophagic degradation of cytosolic mitochondrial DNA during sterile innate immune responses.
Cell Rep
December 2024
Cellular Degradation Biology Center and Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; Convergence Research Center for Dementia, Seoul National University Medical Research Center, Seoul 110-799, Republic of Korea; AUTOTAC Bio, Inc., Changkkyunggung-ro 254, Jongno-gu, Seoul 03077, Republic of Korea; Ischemic/Hypoxic Disease Institute, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea. Electronic address:
The human body reacts to tissue damage by generating damage-associated molecular patterns (DAMPs) that activate sterile immune responses. To date, little is known about how DAMPs are removed to avoid excessive immune responses. Here, we show that proteasomal dysfunction induces the release of mitochondrial DNA (mtDNA) as a DAMP that activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway and is subsequently degraded through the N-degron pathway.
View Article and Find Full Text PDFProtective effects of adipose-derived stem cells against testicular injury induced after ischemia-reperfusion by regulating autophagy.
Histochem Cell Biol
December 2024
Stem Cell Laboratory, University of Health Sciences Gulhane Health Sciences Institute, Ankara, Turkey.
The damaged organ may experience severe pathological alterations as a result of tissue ischemia-reperfusion (I/R). The study of stem cell-based repair therapies is actively being conducted, and the outcomes and therapeutic potential of these cells are both promising. Autophagy checks protein homeostasis by breaking down huge damaged proteins or organelles.
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