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https://www.readbyqxmd.com/read/28634272/the-secreted-msp-domain-of-c-elegans-vapb-homolog-vpr-1-patterns-the-adult-striated-muscle-mitochondrial-reticulum-via-smn-1
#1
Jessica Schultz, Se-Jin Lee, Tim Cole, Hieu D Hoang, Jack Vibbert, Pauline A Cottee, Michael A Miller, Sung Min Han
The major sperm protein domain (MSPd) has an extracellular signaling function implicated in amyotrophic lateral sclerosis. Secreted MSPds derived from the C. elegans VAPB homolog VPR-1 promote mitochondrial localization to actin-rich I-bands in body wall muscle. Here we show that the nervous system and germ line are key MSPd secretion tissues. MSPd signals are transduced through the CLR-1 Lar-like tyrosine phosphatase receptor. We show that CLR-1 is expressed throughout the muscle plasma membrane, where it is accessible to MSPd within the pseudocoelomic fluid...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28633562/advances-in-imaging-brain-metabolism
#2
Fahmeed Hyder, Douglas L Rothman
Metabolism is central to neuroimaging because it can reveal pathways by which neuronal and glial cells use nutrients to fuel their growth and function. We focus on advanced magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) methods used in brain metabolic studies. (17)O-MRS and (31)P-MRS, respectively, provide rates of oxygen use and ATP synthesis inside mitochondria, whereas (19)F-MRS enables measurement of cytosolic glucose metabolism. Calibrated functional MRI (fMRI), an advanced form of fMRI that uses contrast generated by deoxyhemoglobin, provides maps of oxygen use that track neuronal firing across brain regions...
June 21, 2017: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/28630416/hif-1-mediated-suppression-of-mitochondria-electron-transport-chain-function-confers-resistance-to-lidocaine-induced-cell-death
#3
Akihisa Okamoto, Chisato Sumi, Hiromasa Tanaka, Munenori Kusunoki, Teppei Iwai, Kenichiro Nishi, Yoshiyuki Matsuo, Hiroshi Harada, Keizo Takenaga, Hidemasa Bono, Kiichi Hirota
The local anesthetic lidocaine induces cell death by altering reactive oxygen species (ROS) generation and mitochondrial electron transport chain function. Because hypoxia-inducible factor 1 (HIF-1) is involved in determining oxygen metabolism and mitochondria function, we investigated the involvement of HIF-1 activity in lidocaine-induced cell death. We investigated the role of HIF activation on lidocaine-induced caspase activation and cell death in renal cell-derived RCC4 cells lacking functional von Hippel-Lindau (VHL) protein...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28628299/dihydropyrimidine-thiones-and-clioquinol-synergize-to-target-%C3%AE-amyloid-cellular-pathologies-through-a-metal-dependent-mechanism
#4
Daniel F Tardiff, Lauren E Brown, Xiaohui Yan, Richard Trilles, Nathan T Jui, M Inmaculada Barrasa, Kim A Caldwell, Guy A Caldwell, Scott E Schaus, Susan Lindquist
The lack of therapies for neurodegenerative diseases arises from our incomplete understanding of their underlying cellular toxicities and the limited number of predictive model systems. It is critical that we develop approaches to identify novel targets and lead compounds. Here, a phenotypic screen of yeast proteinopathy models identified dihydropyrimidine-thiones (DHPM-thiones) that selectively rescued the toxicity caused by β-amyloid (Aβ), the peptide implicated in Alzheimer's disease. Rescue of Aβ toxicity by DHPM-thiones occurred through a metal-dependent mechanism of action...
June 19, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28627365/mitochondria-metabolic-reprogramming-in-the-formation-of-neurons-from-peripheral-cells-cause-or-consequence-and-the-implications-to-their-utility
#5
REVIEW
Gary E Gibson, Ankita Thakkar
The induction of pluripotent stem cells (iPSC) from differentiated cells such as fibroblasts and their subsequent conversion to neural progenitor cells (NPC) and finally to neurons is intriguing scientifically, and its potential to medicine nearly infinite, but unrealized. A better understanding of the changes at each step of the transformation will enable investigators to use them better to model neurological disease. Each step of conversion from a differentiated cell to an iPSC to a NPC to neurons requires large changes in glycolysis including aerobic glycolysis, the pentose shunt, the tricarboxylic acid cycle, the electron transport chain and in the production of reactive oxygen species (ROS)...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28623368/regulation-of-sub-compartmental-targeting-and-folding-properties-of-the-prion-like-protein-shadoo
#6
Anna Pepe, Rosario Avolio, Danilo Swann Matassa, Franca Esposito, Lucio Nitsch, Chiara Zurzolo, Simona Paladino, Daniela Sarnataro
Shadoo (Sho), a member of prion protein family, has been shown to prevent embryonic lethality in Prnp (0/0) mice and to be reduced in the brains of rodents with terminal prion diseases. Sho can also affect PrP structural dynamics and can increase the prion conversion into its misfolded isoform (PrP(Sc)), which is amyloidogenic and strictly related to expression, intracellular localization and association of PrP(C) to lipid rafts. We reasoned that if Sho possesses a natural tendency to convert to amyloid-like forms in vitro, it should be able to exhibit "prion-like" properties, such as PK-resistance and aggregation state, also in live cells...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623098/acquired-inhibition-of-microrna-124-protects-against-spinal-cord-ischemia-reperfusion-injury-partially-through-a-mitophagy-dependent-pathway
#7
Kun Liu, Lihui Yan, Xiaojing Jiang, Yang Yu, Hongbo Liu, Tianxiang Gu, Enyi Shi
OBJECTIVE: Mitophagy results in selective clearance of damaged mitochondria. We investigated whether mitophagy was involved in the neuroprotection by inhibiting microRNA (miRNA)-124 on ischemic spinal cords. METHODS: Inhibition of miRNA-124 was conducted by intrathecal injection of lentivirus vectors containing antagomiR-124. Spinal cord ischemia was induced in rats by crossclamping the descending aorta just distal to the left subclavian artery for 14 minutes. Hind-limb motor function was assessed with the motor deficit index (MDI)...
May 23, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28622300/the-als-linked-e102q-mutation-in-sigma-receptor-1-leads-to-er-stress-mediated-defects-in-protein-homeostasis-and-dysregulation-of-rna-binding-proteins
#8
Alice Dreser, Jan Tilmann Vollrath, Antonio Sechi, Sonja Johann, Andreas Roos, Alfred Yamoah, Istvan Katona, Saeed Bohlega, Dominik Wiemuth, Yuemin Tian, Axel Schmidt, Jörg Vervoorts, Marc Dohmen, Cordian Beyer, Jasper Anink, Eleonora Aronica, Dirk Troost, Joachim Weis, Anand Goswami
Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons (MNs) and their target muscles. Misfolded proteins which often form intracellular aggregates are a pathological hallmark of ALS. Disruption of the functional interplay between protein degradation (ubiquitin proteasome system and autophagy) and RNA-binding protein homeostasis has recently been suggested as an integrated model that merges several ALS-associated proteins into a common pathophysiological pathway...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28622174/insufficient-astrocyte-derived-brain-derived-neurotrophic-factor-contributes-to-propofol-induced-neuron-death-through-akt-glycogen-synthase-kinase-3%C3%AE-mitochondrial-fission-pathway
#9
Yanan Liu, Yasheng Yan, Yasuyoshi Inagaki, Sarah Logan, Zeljko J Bosnjak, Xiaowen Bai
BACKGROUND: Growing animal evidence demonstrates that prolonged exposure to propofol during brain development induces widespread neuronal cell death, but there is little information on the role of astrocytes. Astrocytes can release neurotrophic growth factors such as brain-derived neurotrophic factor (BDNF), which can exert the protective effect on neurons in paracrine fashion. We hypothesize that during propofol anesthesia, BDNF released from developing astrocytes may not be sufficient to prevent propofol-induced neurotoxicity...
July 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28621566/glutamate-dehydrogenase-is-essential-to-sustain-neuronal-oxidative-energy-metabolism-during-stimulation
#10
Michaela C Hohnholt, Vibe H Andersen, Jens V Andersen, Sofie K Christensen, Melis Karaca, Pierre Maechler, Helle S Waagepetersen
The enzyme glutamate dehydrogenase (GDH; Glud1) catalyzes the (reversible) oxidative deamination of glutamate to α-ketoglutarate accompanied by a reduction of NAD(+) to NADH. GDH connects amino acid, carbohydrate, neurotransmitter and oxidative energy metabolism. Glutamine is a neurotransmitter precursor used by neurons to sustain the pool of glutamate, but glutamine is also vividly oxidized for support of energy metabolism. This study investigates the role of GDH in neuronal metabolism by employing the Cns- Glud1(-/-) mouse, lacking GDH in the brain (GDH KO) and metabolic mapping using (13)C-labelled glutamine and glucose...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28619096/presenilins-regulate-synaptic-plasticity-and-mitochondrial-calcium-homeostasis-in-the-hippocampal-mossy-fiber-pathway
#11
Sang Hun Lee, David Lutz, Mohanad Mossalam, Vadim Y Bolshakov, Michael Frotscher, Jie Shen
BACKGROUND: Presenilins play a major role in the pathogenesis of Alzheimer's disease, in which the hippocampus is particularly vulnerable. Previous studies of Presenilin function in the synapse, however, focused exclusively on the hippocampal Schaffer collateral (SC) pathway. Whether Presenilins play similar or distinct roles in other hippocampal synapses is unknown. METHODS: To investigate the role of Presenilins at mossy fiber (MF) synapses we performed field and whole-cell electrophysiological recordings and Ca(2+) imaging using acute hippocampal slices of postnatal forebrain-restricted Presenilin conditional double knockout (PS cDKO) and control mice at 2 months of age...
June 15, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28614981/nuclear-encoded-mitochondrial-mrnas-a-powerful-force-in-axonal-growth-and-development
#12
Jenna R Gale, Armaz Aschrafi, Anthony E Gioio, Barry B Kaplan
Axons, their growth cones, and synaptic nerve terminals are neuronal subcompartments that have high energetic needs. As such, they are enriched in mitochondria, which supply the ATP necessary to meet these demands. To date, a heterogeneous population of nuclear-encoded mitochondrial mRNAs has been identified in distal axons and growth cones. Accumulating evidence suggests that the local translation of these mRNAs is required for mitochondrial maintenance and axonal viability. Here, we review evidence that suggests a critical role for axonal translation of nuclear-encoded mitochondrial mRNAs in axonal growth and development...
June 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/28614042/bnip3l-nix-dependent-mitophagy-regulates-cell-differentiation-via-metabolic-reprogramming
#13
Lorena Esteban-Martínez, Patricia Boya
Macroautophagy/autophagy is the process by which cellular components are degraded and recycled within the lysosome. These components include mitochondria, the selective degradation of which is known as mitophagy. Mitochondria are dynamic organelles that constantly adapt their morphology, function, and number to accommodate the metabolic needs of the cell. Extensive metabolic reconfiguration occurs during cell differentiation, when mitochondrial activity increases in most cell types. However, our data demonstrate that during physiological retinal ganglion cell (RGC) development, mitophagy-dependent metabolic reprogramming towards glycolysis regulates numbers of RGCs, which are the first neurons to differentiate in the retina and whose axons form the optic nerve...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28611589/mitochondrial-effects-of-pgc-1alpha-silencing-in-mpp-treated-human-sh-sy5y-neuroblastoma-cells
#14
Qinyong Ye, Chun Chen, Erwang Si, Yousheng Cai, Juhua Wang, Wanling Huang, Dongzhu Li, Yingqing Wang, Xiaochun Chen
The dopaminergic neuron degeneration and loss that occurs in Parkinson's disease (PD) has been tightly linked to mitochondrial dysfunction. Although the aged-related cause of the mitochondrial defect observed in PD patients remains unclear, nuclear genes are of potential importance to mitochondrial function. Human peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) is a multi-functional transcription factor that tightly regulates mitochondrial biogenesis and oxidative capacity. The goal of the present study was to explore the potential pathogenic effects of interference by the PGC-1α gene on N-methyl-4-phenylpyridinium ion (MPP(+))-induced SH-SY5Y cells...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28611284/activation-of-the-atf2-creb-pgc-1%C3%AE-pathway-by-metformin-leads-to-dopaminergic-neuroprotection
#15
Hojin Kang, Rin Khang, Sangwoo Ham, Ga Ram Jeong, Hyojung Kim, Minkyung Jo, Byoung Dae Lee, Yun Il Lee, Areum Jo, Chi Hu Park, Hyein Kim, Jeongkon Seo, Sun Ha Paek, Yun-Song Lee, Jeong-Yun Choi, Yunjong Lee, Joo-Ho Shin
Progressive dopaminergic neurodegeneration is responsible for the canonical motor deficits in Parkinson's disease (PD). The widely prescribed anti-diabetic medicine metformin is effective in preventing neurodegeneration in animal models; however, despite the significant potential of metformin for treating PD, the therapeutic effects and molecular mechanisms underlying dopaminergic neuroprotection by metformin are largely unknown.In this study, we found that metformin induced substantial proteomic changes, especially in metabolic and mitochondrial pathways in the substantia nigra (SN)...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28610459/an-automated-pipeline-for-mitochondrial-segmentation-on-atum-sem-stacks
#16
Weifu Li, Hao Deng, Qiang Rao, Qiwei Xie, Xi Chen, Hua Han
It is possible now to look more closely into mitochondrial physical structures due to the rapid development of electron microscope (EM). Mitochondrial physical structures play important roles in both cellular physiology and neuronal functions. Unfortunately, the segmentation of mitochondria from EM images has proven to be a difficult and challenging task, due to the presence of various subcellular structures, as well as image distortions in the sophisticated background. Although the current state-of-the-art algorithms have achieved some promising results, they have demonstrated poor performances on these mitochondria which are in close proximity to vesicles or various membranes...
May 26, 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/28608291/iron-induced-generation-of-mitochondrial-ros-depends-on-ampk-activity
#17
Hui Huang, Jun Chen, Huiru Lu, Mengxue Zhou, Zhifang Chai, Yi Hu
Deregulated iron homeostasis is generally believed to be implicated in neurodegenerative diseases, including Parkinson's disease. Nevertheless, it is not fully understood how iron overload can elicit neuronal cell damage. Here we examined mitochondrial reactive oxygen species (ROS) levels in human dopaminergic neuroblastoma SH-SY5Y cells upon iron exposure. A relatively high concentration of iron could significantly increase mitochondrial ROS levels in SH-SY5Y cells. Pharmacological activation of AMP-activated protein kinase (AMPK) almost completely inhibited the effect of iron on mitochondrial ROS...
June 12, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28601083/disruption-of-functional-activity-of-mitochondria-during-mtt-assay-of-viability-of-cultured-neurons
#18
A M Surin, R R Sharipov, I A Krasil'nikova, D P Boyarkin, O Yu Lisina, L R Gorbacheva, A V Avetisyan, V G Pinelis
The MTT assay based on the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium in the cell cytoplasm to a strongly light absorbing formazan is among the most commonly used methods for determination of cell viability and activity of NAD-dependent oxidoreductases. In the present study, the effects of MTT (0.1 mg/ml) on mitochondrial potential (ΔΨm), intracellular NADH, and respiration of cultured rat cerebellum neurons and isolated rat liver mitochondria were investigated. MTT caused rapid quenching of NADH autofluorescence, fluorescence of MitoTracker Green (MTG) and ΔΨm-sensitive probes Rh123 (rhodamine 123) and TMRM (tetramethylrhodamine methyl ester)...
June 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28600320/limited-distal-organelles-and-synaptic-function-in-extensive-monoaminergic-innervation
#19
Juan Tao, Dinara Bulgari, David L Deitcher, Edwin S Levitan
Organelles such as neuropeptide-containing dense-core vesicles (DCVs) and mitochondria travel down axons to supply synaptic boutons. DCV distribution among en passant boutons in small axonal arbors is mediated by circulation with bidirectional capture. However, it is not known how organelles are distributed in extensive arbors associated with volume transmission and neuromodulation by monoamines and neuropeptides and mammalian dopamine neuron vulnerability. Therefore, we studied presynaptic organelle distribution in Drosophila octopamine neurons that innervate ∼20 muscles with ∼1500 boutons...
June 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28600240/neuron-segmentation-with-high-level-biological-priors
#20
Niko Krasowski, Thorsten Beier, Graham Knott, Ullrich Koethe, Fred Hamprecht, Anna Kreshuk
We present a novel approach to the problem of neuron segmentation in image volumes acquired by Electron Microscopy. Existing methods such as agglomerative or correlation clustering rely solely on boundary evidence and have problems where such evidence is lacking (e.g. incomplete staining) or ambiguous (e.g. co-located cell and mitochondria membranes). We investigate if these difficulties can be overcome by means of sparse region appearance cues that differentiate between pre- and postsynaptic neuron segments in mammalian neural tissue...
June 6, 2017: IEEE Transactions on Medical Imaging
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