Transmembrane protein 166 (TMEM166) is a lysosomal/endoplasmic reticulum (ER)-associated protein found in different species where it functions as a regulator of programmed cell death through autophagy and apoptosis. It is expressed in a variety of normal tissues and organs, and it is involved in a wide variety of physiological and pathological processes, including cancers, infection, autoimmune diseases, and neurodegenerative diseases. Previous studies indicated that TMEM166 is associated with autophagosomal membrane development. TMEM166 can cause lysosomal membrane permeabilization (LMP) leading to the release of proteolytic enzymes, e.g., cathepsins, that may cause potential mitochondrial membrane damage, which triggers several autophagic and apoptotic events. A low level of TMEM166 expression is also found in tumors, while high level of TMEM166 is found in brain ischemia. In addition, loss of TMEM166 leads to impaired NSC self-renewal and differentiation along with a decrease in autophagy. These findings offer a comprehensive understanding of the pathways involved in the role of TMEM166 in programmed cell death and treatment of various diseases.
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http://dx.doi.org/10.2174/0929866527666201002150316 | DOI Listing |
Sao Paulo Med J
January 2025
Associate Professor, Department of Nephrology, Ankara Bilkent City Hospital, Ankara, Turkey.
Background: Insulin resistance often occurs in patients with chronic kidney disease (CKD) owing to mineral and bone metabolism disorders. Fibroblast growth factor (FGF)-23 and soluble klotho (s-KL) play crucial roles in linking CKD with mineral and bone metabolism.
Objective: This study aimed to examine the relationship between insulin resistance and FGF-23 and s-KL in patients with non-diabetic pre-dialysis patients with CKD.
J Appl Oral Sci
January 2025
Ningde Hospital Affiliated to Ningde Normal University, Department of Stomatology, Fujian, China.
Objective: This study aimed to investigate the role of transmembrane emp24 domain-containing protein 2 (TMED2) in oral squamous cell carcinoma (OSCC).
Methodology: A bioinformatics analysis was first conducted to explore TMED2 expression in OSCC and its relation with overall survival. The analysis results were further verified by assessing TMED2 expression levels in human normal oral keratinocyte cells and human OSCC cell lines using quantitative real-time polymerase chain reaction and the Western blot.
Sci Transl Med
January 2025
University of Strasbourg, INSERM, Strasbourg Translational Neuroscience & Psychiatry STEP-CRBS, UMR-S 1329, 67000 Strasbourg, France.
Sleep alterations have been described in several neurodegenerative diseases yet are currently poorly characterized in amyotrophic lateral sclerosis (ALS). This study investigates sleep macroarchitecture and related hypothalamic signaling disruptions in ALS. Using polysomnography, we found that both patients with ALS as well as asymptomatic and mutation carriers exhibited increased wakefulness and reduced non-rapid eye movement sleep.
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Pancreatic ductal adenocarcinoma (PDAC) driven by the mutation presents a formidable health challenge because of limited treatment options. MRTX1133 is a highly selective and first-in-class KRAS-G12D inhibitor under clinical development. Here, we report that the advanced glycosylation end product-specific receptor (AGER) plays a key role in mediating MRTX1133 resistance in PDAC cells.
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January 2025
Department of Medicine, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, CO, USA.
Programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) interactions are targets for immunotherapies aimed to reinvigorate T cell function. Recently, it was documented that PD-L1 regulates dendritic cell (DC) migration through intracellular signaling events. In this study, we find that both preclinical murine and clinically available human PD-L1 antibodies limit DC migration.
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