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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Contributors : Deng-Feng Zhang ; Yu Fan ; Min Xu ; Yong-Gang YaoSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensWe identified a rare coding variant (p.K420Q) in the complement component 7 (C7) gene affecting the risk of Alzheimer's disease. To investigate the cellular effects of the mutant, we performed RNA-seq in cell line overexpression wilt-type and mutant C7. U251 glioma cells with stable expression of mutant APP (K670N/M671L) (U251-APP cells), which produce A β42 under Dox inducing, were used as the model cell. Total RNA of U251-APP cells overexpressing wild type and mutant...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
AbstractThe current review highlights the evidence supporting the use of ketogenic diet therapies in the management of a growing number of neurological disorders in adults. An overview of the scientific literature supporting posited mechanisms of therapeutic efficacy is presented including effects on neurotransmission, oxidative stress, and neuro-inflammation. The clinical evidence supporting ketogenic diet use in the management of adult epilepsy, malignant glioma, Alzheimer ’s disease, migraine headache, motor neuron disease, and other neurologic disorders is highlighted and reviewed. Lastly, common adverse effects ...
Source: Neurotherapeutics - Category: Neurology Source Type: research
Publication date: Available online 4 July 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research Author(s): Bing Sun, Ping Fan, Meijian Liao, Yaou Zhang Autophagy dysregulation has emerged in age-related neurological diseases (Ulland et al.; Matheoud et al.; Ashkenazi et al. [1–3]). 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. [4–6]). Glia constitute the brain immune system and ingest extracellular A&bet...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research
Abstract Neurotoxic metals have been implicated in the pathogenesis of multiple sclerosis, neurodegenerative disorders and brain tumours but studies of the location of heavy metals in human brains are rare. In a man who injected himself with metallic mercury the cellular location of mercury in his brain was studied after 5 months of continuous exposure to inorganic mercury arising from metallic mercury deposits in his organs. Paraffin sections from the primary motor and sensory cortices and the locus ceruleus in the pons were stained with autometallography to detect inorganic mercury and combined with glial f...
Source: Biometals - Category: Biochemistry Authors: Tags: Biometals Source Type: research
Abstract Septins are a conserved family of cytoskeletal GTPases present in different organisms, including yeast, drosophila, Caenorhabditis elegans and humans. In humans, septins are involved in various cellular processes, including exocytosis, apoptosis, leukemogenesis, carcinogenesis and neurodegeneration. Septin 7 is unique out of 13 human septins. Mammalian septin 6, septin 7, septin 2 and septin 9 coisolate together in complexes to form the core unit for the generation of the septin filaments. Physiological septin filaments are hetero-oligomeric complexes consisting of core septin hexamers and octamers. Furth...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Publication date: 1 June 2018 Source:Materials Science and Engineering: C, Volume 87 Author(s): Chen Fu, Yonggang Xiang, Xiaorong Li, Ailing Fu For successful theranosis of brain diseases, limited access of therapeutic molecules across blood-brain barrier (BBB) needs be overcome in brain delivery. Currently, peptide derivatives of rabies virus glycoprotein (RVG) have been exploited as delivery ligands to transport nanocarriers across BBB and specifically into the brain. The targeting peptides usually conjugate to the nanocarrier surface, and the cargoes, including siRNA, miRNA, DNA, proteins and small molecular chemicals,...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research
Epimedium koreanum Nakai inhibits PMA-induced cancer cell migration and invasion by modulating NF-κB/MMP-9 signaling in monomorphic malignant human glioma cells. Oncol Rep. 2017 Dec;38(6):3619-3631 Authors: Lee W, Nam JH, Cho HJ, Lee JY, Cho WK, Kim Υ, We YM, Ma JY, Hoe HS Abstract Previously, we showed that the herbal extract EYK (Epimedium koreanum Nakai) can regulate the immune response. Other studies showed that EYK has beneficial effects in human lung cancer, angiogenesis and Alzheimer's disease (AD). However, it remains unknown whether EYK can affect cancer cell migration and invasi...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
" The role of CXCR3 in neurological diseases". Curr Neuropharmacol. 2017 Nov 09;: Authors: Zhou YQ, Liu DQ, Chen SP, Sun J, Zhou XR, Xing C, Ye DW, Tian YK Abstract Neurological diseases have become an obvious challenge due to insufficient therapeutic intervention. Therefore, novel drugs for various neurological disorders are in desperate need. Recently, compelling evidence has demonstrated that chemokine receptor CXCR3, which is a G protein-coupled receptor in the CXC chemokine receptor family, may play a pivotal role in the development of neurological diseases. The expression level of CXCR...
Source: Current Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Neuropharmacol Source Type: research
In conclusion, CAVD is highly prevalent. Long understood as a passive process, it is now known to be complex and one which involves pathophysiological mechanisms similar to those of atherosclerosis. Understanding these mechanisms could help to establish new therapeutic targets that might allow us to halt or at least slow down the progression of the disease. Early Steps in the Tissue Engineering of Intervertebral Discs https://www.fightaging.org/archives/2017/08/early-steps-in-the-tissue-engineering-of-intervertebral-discs/ In this paper, researchers report on progress towards the manufacture of interver...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Each year, the SENS Research Foundation accepts a group of young life science academics and puts them to work on projects in aging research, both at the foundation and in allied laboratories, creating ties between research groups that can help to advance the state of the art. This year's batch has worked on a diverse set of projects that spread out beyond core SENS initiatives such as allotopic expression of mitochondrial genes. Reading through their projects is a reminder that a great deal can be accomplished these days given a small team, a little funding, and an equipped laboratory. Progress in medical research is no lo...
Source: Fight Aging! - Category: Research Authors: Tags: Healthy Life Extension Community Source Type: blogs
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