Modeling endophilin-mediated Aβ disposal in glioma cells

Publication date: Available online 4 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Bing Sun, Ping Fan, Meijian Liao, Yaou ZhangAbstractAutophagy dysregulation has emerged in age-related neurological diseases (Ulland et al.; Matheoud et al.; Ashkenazi et al. [[1], [2], [3]]). Alzheimer Disease (AD), the most common progressive neurodegenerative disorder, is characterized by the accumulation of amyloid-β (Aβ) plaques caused by aberrant Aβ metabolism (Qiang et al.; Sevigny et al.; Ittner et al. [[4], [5], [6]]). Glia constitute the brain immune system and ingest extracellular Aβ for degradation via the autophagy-lysosome machinery (Ries and Sastre; Cho et al. [7, 8]). Here, we model the molecular rationale for this clearance process in glioma cells by showing that miR34a inhibits autophagy-mediated disposal of Aβ fibrils and identifying two novel direct targets of miR34a, endophilin-3 and cathepsin B (CTSB, a previously reported enzyme for Aβ degrading (Sun et al. [9])). Bioinformatics analyses revealed that endophilin-3 expresses at a significantly lower level in neurodegenerative diseases. Its gain-of-function substantially promotes both uptake and degradation of Aβ while small interfering RNA (siRNA)-mediated endophilin-3 knockdown slowed down Aβ clearance and blocked autolysosome formation. Mechanistically, gene ontology (GO) analysis of the endophilin-3 interactome identified by mass spectrom...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research

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We reported DEGs with a nominal p-value of 0.8. The network construction was created using blockwiseModules function for consideration of computer efficiency. The module detection criteria were as follows: minimum module size of 50, deepsplit of 4, and merge threshold of 0.25. The merged modules were then summarized with module eigengene (ME) correlations>0.75. MEs were defined by their first principal component and were labeled with different colors as module names in the Results section. After the modules were generated, we conducted different enrichment analysis to explore the functional interpretation of genes withi...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
In this study, the lung adenocarcinoma patients and granuloma patients were treated as positive samples and negative samples, respectively. We used weighted accuracy to evaluate the RIPPER prediction performance, i.e., the average of the accuracies of positive samples and negative samples. Results The Discriminative MicroRNAs Between Lung Adenocarcinoma and Granuloma Patients in Whole Plasma, EV, and EV-Free Plasma The miRNA expression profiles of lung adenocarcinoma and granuloma patients in whole plasma, EV and EV-free plasma were analyzed separately. In whole plasma, the top 10 discriminative miRNAs were hsa-miR-223-...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
In conclusion, while rs-fMRI use in clinical neuroradiology practice is limited, enthusiasm appears to be quite high and there are several possible avenues in which further research and development may facilitate its penetration into clinical practice. Introduction Techniques for quantifying spatial and temporal brain activity have developed rapidly since the first demonstrations that MRI could be used to measure modulations in blood oxygen level dependent (BOLD) tissue contrast (1). The observation that MRI could be used to monitor temporally correlated low-frequency activity fluctuations in spatially remote brain a...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Gui-Jiang Wei1,2, Ming-Qing Yuan1, Li-He Jiang1, Yu-Lan Lu3, Chun-Hong Liu3, Hong-Cheng Luo3, Hua-Tuo Huang3, Zong-Quan Qi1* and Ye-Sheng Wei1,2* 1Department of Cell Biology, Medical College of Guangxi University, Nanning, China 2Department of Medical Laboratory, Affiliated Hospital of Guilin Medical University, Guilin, China 3Department of Medical Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China miRNAs are small non-coding RNAs modulating gene expression, and variants in miRNA genes are involved in the pathogenesis of ischemic stroke (IS). However, the effect of mi...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Silvia Pregnolato1*, Elavazhagan Chakkarapani1, Anthony R. Isles2 and Karen Luyt1 1Department of Neonatal Neurology, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom 2Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom Preterm birth complications are the leading cause of child death worldwide and a top global health priority. Among the survivors, the risk of life-long disabilities is high, including cerebral palsy and impairment of movement, cognition, and behavior. U...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroinfla...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Abstract Alzheimer disease (AD) is the most common neurodegenerative disease. An imbalance between the production and clearance of Aβ (amyloid beta) is considered to be actively involved in AD pathogenesis. Macroautophagy/autophagy is a major cellular pathway leading to the removal of aggregated proteins, and upregulation of autophagy represents a plausible therapeutic strategy to combat overproduction of neurotoxic Aβ. PPARA/PPARα (peroxisome proliferator activated receptor alpha) is a transcription factor that regulates genes involved in fatty acid metabolism and activates hepatic autophagy. We h...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research
In this study, neural-inducing ability of curcumin was explored by using human pluripotent embryonal carcinoma cells, NTERA2 cells. The cells were induced toward neural lineage with curcumin and were compared with a standard neutralizing agent (retinoic acid). It was found that, after 14 days of the induction by curcumin, NTERA2 cells showed neuronal morphology and expressed neural-specific genes, including NeuroD, TUJ1, and PAX6. Importantly, curcumin activated neurogenesis of NTERA2 cells via the activation of autophagy, since autophagy-related genes, such as LC3, LAMP1, and ATG5, were upregulated along with the expressi...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
Publication date: Available online 14 February 2019Source: NeuroscienceAuthor(s): Bárbara Paranhos Coelho, Mariana Maier Gaelzer, Fernanda dos Santos Petry, Juliana Bender Hoppe, Vera Maria Treis Trindade, Christianne G. Salbego, Fátima T.C.R. GumaAbstractSeveral studies have demonstrated the antitumor effect of doxazosin, an α1-adrenergic blocker, against glioma and breast, bladder and prostate cancers. Doxazosin is also being evaluated as a treatment for posttraumatic stress disorder and alcoholism, and α1-adrenergic blockers have been linked to neuroprotection in neurodegenerative disorders, su...
Source: Neuroscience - Category: Neuroscience Source Type: research
In this study, we sought to examine the role of FABP7 in primary mouse astrocytes, focusing on its protective effect against reactive oxygen species (ROS) stress. In FABP7 knockout (KO) astrocytes, ROS induction significantly decreased LD accumulation, elevated ROS toxicity, and impaired thioredoxin (TRX) but not peroxiredoxin 1 (PRX1) signalling compared to ROS induction in wild-type astrocytes. Consequently, activation of apoptosis signalling molecules, including p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and increased expression of cleaved caspase ...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
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