Although dyslipidemia in the brain has been implicated in neurodegenerative disorders, the molecular mechanisms underlying its pathogenesis have been largely unclear. PDZD8 is a lipid transfer protein and mice deficient in PDZD8 (PDZD8-KO mice) manifest abnormal accumulation of cholesteryl esters (CEs) in the brain due to impaired lipophagy, the degradation system of lipid droplets. Here we show the detailed mechanism of PDZD8-dependent lipophagy. PDZD8 transports cholesterol to lipid droplets (LDs), and eventually promotes fusion of LDs and lysosomes. In addition, PDZD8-KO mice exhibit growth retardation, hyperactivity, reduced anxiety and fear, increased sensorimotor gating, and impaired cued fear conditioned memory and working memory. These results indicate that abnormal CE accumulation in the brain caused by PDZD8 deficiency affects emotion, cognition and adaptive behavior, and that PDZD8 plays an important role in the maintenance of brain function through lipid metabolism.
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http://dx.doi.org/10.1186/s13041-023-01002-4 | DOI Listing |
Neurochem Res
January 2025
Department of Orthopaedics, Tianjin Hospital, Tianjin University, Tianjin, China.
Neuropathic pain (NP) imposes a significant burden on individuals, manifesting as nociceptive anaphylaxis, hypersensitivity, and spontaneous pain. Previous studies have shown that traumatic stress in the nervous system can lead to excessive production of hydrogen sulfide (HS) in the gut. As a toxic gas, it can damage the nervous system through the gut-brain axis.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, C11, 75185, Uppsala, Sweden.
The existence of transmissible amyloid fibril strains has long intrigued the scientific community. The strain theory originates from prion disorders, but here, we provide evidence of strains in systemic amyloidosis. Human AA amyloidosis manifests as two distinct clinical phenotypes called common AA and vascular AA.
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January 2025
Key Laboratory for Stem Cells and Tissue Engineering Ministry of Education, Guangdong Provincial Key Laboratory of Brain Function and Disease, Institute of Spinal Cord Injury, Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Neuromuscular diseases usually manifest as abnormalities involving motor neurons, neuromuscular junctions, and skeletal muscle (SkM) in postnatal stage. Present in vitro models of neuromuscular interactions require a long time and lack neuroglia involvement. Our study aimed to construct rodent bioengineered spinal cord neural network-skeletal muscle (NN-SkM) assembloids to elucidate the interactions between spinal cord neural stem cells (SC-NSCs) and SkM cells and their biological effects on the development and maturation of postnatal spinal cord motor neural circuits.
View Article and Find Full Text PDFJ Adv Res
January 2025
Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Clinical Research and Experimental Center, Department of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China; Department of Clinical Laboratory, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University. Guangzhou 510120, China. Electronic address:
Introduction: Developing strategies to improve the therapeutic efficacy of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in autoimmune diseases have garnered increased attention.
Objectives: To evaluate whether rapamycin-induced autophagy within the systemic lupus erythematosus (SLE) inflammatory microenvironment (Rapa-SLE) augments the therapeutic effects of MSC-derived EVs in SLE.
Methods: The therapeutic potential of the resulting EVs (Rapa-SLE-EV) was assessed in MRL/lpr mice.
Biochem Cell Biol
January 2025
Department of Histology and Embryology, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, China.
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with high mortality and limited treatment options. While single-dose bleomycin-induced models are commonly used to investigate the pathogenesis of IPF, they fail to adequately replicate the complex pathological features in human patients, thereby hindering comprehensive investigations. Previous studies utilizing repetitive bleomycin injections have demonstrated a closer resemblance to human IPF pathology; however, the time- and resource-intensive nature of this approach presents significant drawbacks.
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