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https://www.readbyqxmd.com/read/29342113/mitochondria-oxidative-stress-and-the-kynurenine-system-with-a-focus-on-ageing-and-neuroprotection
#1
REVIEW
Katalin Sas, Elza Szabó, László Vécsei
In this review, the potential causes of ageing are discussed. We seek to gain insight into the main physiological functions of mitochondria and discuss alterations in their function and the genome, which are supposed to be the central mechanisms in senescence. We conclude by presenting the potential modulating role of the kynurenine pathway in the ageing processes. Mitochondrial dynamics are supposed to have important physiological roles in maintaining cell homeostasis. During ageing, a decrease in mitochondrial dynamics was reported, potentially compromising the function of mitochondria...
January 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29339456/parp-inhibition-prevents-ethanol-induced-neuroinflammatory-signaling-and-neurodegeneration-in-adult-age-rat-brain-slice-cultures
#2
Nuzhath F Tajuddin, Hee-Yong Kim, Michael A Collins
Utilizing rat adult-age hippocampal-entorhinal cortical (HEC) slice cultures we examined the role of poly [ADP-ribose] polymerase (PARP) in binge ethanol's brain inflammatory and neurodegenerative mechanisms. Activated by DNA strand breaks, PARP (principally PARP1 in brain) promotes DNA repair via poly [ADP-ribose] (PAR) products, but PARP overactivation triggers regulated neuronal necrosis, e.g., parthanatos. Previously we found that brain PARP1 levels were upregulated by neurotoxic ethanol binges in adult rats and HEC slices, and PARP inhibitor PJ34 abrogated slice neurodegeneration...
January 16, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29339192/tissue-specific-differences-in-mitochondrial-dna-maintenance-and-expression
#3
Elena Herbers, Nina J Kekäläinen, Anu Hangas, Jaakko L Pohjoismäki, Steffi Goffart
The different cell types of multicellular organisms have specialized physiological requirements, affecting also their mitochondrial energy production and metabolism. The genome of mitochondria is essential for mitochondrial oxidative phosphorylation (OXHPOS) and thus plays a central role in many human mitochondrial pathologies. Disorders affecting mitochondrial DNA (mtDNA) maintenance are typically resulting in a tissue-specific pattern of mtDNA deletions and rearrangements. Despite this role in disease as well as a biomarker of mitochondrial biogenesis, the tissue-specific parameters of mitochondrial DNA maintenance have been virtually unexplored...
January 12, 2018: Mitochondrion
https://www.readbyqxmd.com/read/29339103/comparative-review-of-adult-midbrain-and-striatum-neurogenesis-with-classical-neurogenesis
#4
REVIEW
Parisa Farzanehfar
Parkinson's Disease (PD) motor symptoms are caused by loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) of the midbrain. Dopamine cell replacement therapy (DA CRT), either by cell transplantation or endogenous repair, has been a potential treatment to replace dead cells and improve PD motor symptoms. Adult midbrain and striatum have been studied for many years to find evidence of neurogenesis. Although the literature is controversial, recent research has revived the possibility of neurogenesis here...
January 12, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29338388/novel-fusion-protein-targeting-mitochondrial-dna-improves-pancreatic-islet-functional-potency-and-islet-transplantation-outcomes
#5
Juan S Danobeitia, Peter J Chlebeck, Inna Shokolenko, Xiaobo Ma, Glenn Wilson, Luis A Fernandez
Long-term graft survival is an ongoing challenge in the field of islet transplantation. With the growing demand for transplantable organs, therapies to improve organ quality and reduce the incidence of graft dysfunction are of paramount importance. We evaluated the protective role of a recombinant DNA repair protein targeted to mitochondria (Exscien I-III), as a therapeutic agent using a rodent model of pancreatic islet transplantation. We first investigated the effect of therapy on isolated rat islets cultured with pro-inflammatory cytokines (interleukin-1 β, interferon γ, and tumor necrosis factor α) for 48 h and documented a significant reduction in apoptosis by flow cytometry, improved viability by immunofluorescence, and conserved functional potency in vitro and in vivo in Exscien I-III-treated islets...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29338042/a-pharmacological-screen-for-compounds-that-rescue-the-developmental-lethality-of-a-drosophila-atm-mutant
#6
Stacey A Rimkus, David A Wassarman
Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. As an example, conditional loss-of-function ATM alleles in flies cause progressive neurodegeneration through activation of the innate immune response...
2018: PloS One
https://www.readbyqxmd.com/read/29335358/sox2-is-essential-for-oligodendroglial-proliferation-and-differentiation-during-postnatal-brain-myelination-and-cns-remyelination
#7
Sheng Zhang, Xiaoqing Zhu, Xuehong Gui, Christopher Croteau, Lanying Song, Jie Xu, Aijun Wang, Peter Bannerman, Fuzheng Guo
In the central nervous system (CNS), myelination and remyelination depend on the successful progression and maturation of oligodendroglial lineage cells including proliferation and differentiation of oligodendroglial progenitor cells (OPCs). Previous studies have reported that Sox2 transiently regulates oligodendrocyte (OL) differentiation in the embryonic and perinatal spinal cord and appears dispensable for myelination in the postnatal spinal cord. However, the role of Sox2 in OL development in the brain has yet to be defined...
January 15, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29334295/neuritin-provides-neuroprotection-against-experimental-traumatic-brain-injury-in-rats
#8
Qi Liu, Hang Zhang, Jian Xu, Dong Zhao
Objectives Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Neuritin is a neurotrophic factor that regulates neural growth and development. However, the role of neuritin in alleviating TBI has not been investigated. Methods In this study, Sprague Dawley rats (n = 144) weighing 300 ± 50 g were categorized into control, sham, TBI, and TBI + neuritin groups. The neurological scores and the ultrastructure of cortical neurons, apoptotic cells, and caspase-3 were measured by using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, Western blot analysis, and real-time RT-PCR at various time points post-TBI...
January 15, 2018: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29332257/kynurenic-acid-and-its-derivatives-are-able-to-modulate-the-adhesion-and-locomotion-of-brain-endothelial-cells
#9
Eszter Lajkó, Bernadett Tuka, Ferenc Fülöp, István Krizbai, József Toldi, Kálmán Magyar, László Vécsei, László Kőhidai
The neuroprotective actions of kynurenic acid (KYNA) and its derivatives in several neurodegenerative disorders [characterized by damage to the cerebral endothelium and to the blood-brain barrier (BBB)] are well established. Cell-extracellular matrix (ECM) adhesion is supposedly involved in recovery of impaired cerebral endothelium integrity (endothelial repair). The present work aimed to investigate the effects of KYNA and its synthetic derivatives on cellular behaviour (e.g. adhesion and locomotion) and on morphology of the GP8 rat brain endothelial cell line, modeling the BBB endothelium...
January 13, 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29332196/bioelectronic-modulation-of-carotid-sinus-nerve-activity-in-the-rat-a-potential-therapeutic-approach-for-type-2-diabetes
#10
Joana F Sacramento, Daniel J Chew, Bernardete F Melo, Matteo Donegá, Wesley Dopson, Maria P Guarino, Alison Robinson, Jesus Prieto-Lloret, Sonal Patel, Bradley J Holinski, Nishan Ramnarain, Victor Pikov, Kristoffer Famm, Silvia V Conde
AIMS/HYPOTHESIS: A new class of treatments termed bioelectronic medicines are now emerging that aim to target individual nerve fibres or specific brain circuits in pathological conditions to repair lost function and reinstate a healthy balance. Carotid sinus nerve (CSN) denervation has been shown to improve glucose homeostasis in insulin-resistant and glucose-intolerant rats; however, these positive effects from surgery appear to diminish over time and are heavily caveated by the severe adverse effects associated with permanent loss of chemosensory function...
January 14, 2018: Diabetologia
https://www.readbyqxmd.com/read/29331730/exenatide-exerts-cognitive-effects-by-modulating-the-bdnf-trkb-neurotrophic-axis-in-adult-mice
#11
Manuela Bomba, Alberto Granzotto, Vanessa Castelli, Noemi Massetti, Elena Silvestri, Lorella M T Canzoniero, Annamaria Cimini, Stefano L Sensi
Modulation of insulin-dependent signaling is emerging as a valuable therapeutic tool to target neurodegeneration. In the brain, the activation of insulin receptors promotes cell growth, neuronal repair, and protection. Altered brain insulin signaling participates in the cognitive decline seen in Alzheimer's disease patients and the aging brain. Glucagon-like peptide-1 (GLP-1) regulates insulin secretion and, along with GLP-1 analogues, enhances neurotrophic signaling and counteracts cognitive deficits in preclinical models of neurodegeneration...
December 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29331305/tigar-inhibits-ischemia-reperfusion-induced-inflammatory-response-of-astrocytes
#12
Jieyu Chen, Ding-Mei Zhang, Xing Feng, Jian Wang, Yuan-Yuan Qin, Tian Zhang, Qiao Huang, Rui Sheng, Zhong Chen, Mei Li, Zheng-Hong Qin
The inflammatory response of glial cells contributes to neuronal damage or repair after brain ischemia/reperfusion insult. We previously demonstrated a protective role of TP53-induced glycolysis and apoptosis regulator (TIGAR) in ischemic neuronal injury through increasing the flow of pentose phosphate pathway (PPP). The present study investigated the possible role of TIGAR in ischemia/reperfusion-induced inflammatory response of astrocytes. Male ICR mice were subjected to middle cerebral artery occlusion for 2 h followed by 24 h reperfusion and cultured primary astrocytes were subjected to oxygen glucose deprivation for 9 h followed by 24 h reoxygenation (OGD/R)...
January 10, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29331263/glial-scars-are-permeable-to-the-neurotoxic-environment-of-chronic-stroke-infarcts
#13
Jacob C Zbesko, Thuy-Vi V Nguyen, Tao Yang, Jennifer Beischel Frye, Omar Hussain, Megan Hayes, Amanda Chung, W Anthony Day, Kristina Stepanovic, Maj Krumberger, Justine Mona, Frank M Longo, Kristian P Doyle
Following stroke, the damaged tissue undergoes liquefactive necrosis, a stage of infarct resolution that lasts for months, although the exact length of time is currently unknown. One method of repair involves reactive astrocytes and microglia forming a glial scar to compartmentalize the area of liquefactive necrosis from the rest of the brain. The formation of the glial scar is a critical component of the healing response to stroke, as well as other central nervous system (CNS) injuries. The goal of this study was to evaluate the toxicity of the extracellular fluid present in areas of liquefactive necrosis and determine how effectively it is segregated from the remainder of the brain...
January 10, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29328365/nuclear-gsk3%C3%AE-induces-dna-double-strand-break-repair-by-phosphorylating-53bp1-in-glioblastoma
#14
Yong Yang, Tiantian Lei, Suya Du, Rongsheng Tong, Hailian Wang, Jiao Yang, Juan Huang, Minghan Sun, Yi Wang, Zhi Dong
Glioblastoma is the most malignant and lethal subtype brain tumors with high risk of recurrence and therapeutic resistance. Emerging evidence has indicated that glycogen synthesis kinase 3 (GSK3)β plays oncogenic roles in multiple tumor types; however, the underlying mechanisms remain largely unknown. It has also been demonstrated that p53 binding protein 1 (53BP1) plays a central role in DNA double-strand break (DSB) repair. This study aimed to reveal the significance of GSK3β translocation from the cytoplasm to the nucleus, and to determine whether GSK3β induces DNA DSB repair in the nuclei of glioblastoma cells via phospho-53BP1...
January 4, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29325627/epigenetic-mechanisms-underlying-nervous-system-diseases
#15
Irfan A Qureshi, Mark F Mehler
Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene-gene and gene-environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization; noncoding RNA regulation; and RNA editing...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29323053/roles-of-neural-stem-cells-in-the-repair-of-peripheral-nerve-injury
#16
REVIEW
Chong Wang, Chang-Feng Lu, Jiang Peng, Cheng-Dong Hu, Yu Wang
Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29323026/the-contribution-of-oligodendrocytes-and-oligodendrocyte-progenitor-cells-to-central-nervous-system-repair-in-multiple-sclerosis-perspectives-for-remyelination-therapeutic-strategies
#17
REVIEW
Adriana Octaviana Dulamea
Oligodencrocytes (OLs) are the main glial cells of the central nervous system involved in myelination of axons. In multiple sclerosis (MS), there is an imbalance between demyelination and remyelination processes, the last one performed by oligodendrocyte progenitor cells (OPCs) and OLs, resulting into a permanent demyelination, axonal damage and neuronal loss. In MS lesions, astrocytes and microglias play an important part in permeabilization of blood-brain barrier and initiation of OPCs proliferation. Migration and differentiation of OPCs are influenced by various factors and the process is finalized by insufficient acummulation of OLs into the MS lesion...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29321396/-molecular-and-cellular-mechanisms-underlying-the-sterile-inflammation-after-ischemic-stroke
#18
Takashi Shichita
Inflammation is an essential step for the pathology of ischemic stroke, and is also an important therapeutic target for developing novel therapeutic methods which have a wide therapeutic time window. Since there is no pathogen in the brain, the inflammation will be triggered by some endogenous molecules which are called as danger associated molecular patterns (DAMPs). So far two important DAMPs, high mobility group box 1 (HMGB1) and peroxiredoxin (PRX), have been recently identified in the ischemic brain. HMGB1 exaggerates the disruption of blood brain barrier; on the other hand, PRX activates mononuclear phagocytes and induces the inflammatory cytokine production through the activation of Toll-like receptor 2 (TLR2) and TLR4...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29319405/does-stroke-rehabilitation-really-matter-part-a-proportional-stroke-recovery-in-the-rat
#19
Matthew Strider Jeffers, Sudhir Karthikeyan, Dale Corbett
BACKGROUND: In human upper-limb stroke, initial level of functional impairment or corticospinal tract injury can accurately predict the degree of poststroke recovery, independent of rehabilitation practices. This proportional recovery rule implies that current rehabilitation practices may play little or no role in brain repair, with recovery largely a result of spontaneous biological recovery processes. OBJECTIVE: The present study sought to determine if similar biomarkers predict recovery of poststroke function in rats, indicating that an endogenous biological recovery process might be preserved across mammalian species...
January 1, 2018: Neurorehabilitation and Neural Repair
https://www.readbyqxmd.com/read/29317601/common-basis-for-orofacial-clefting-and-cortical-interneuronopathy
#20
Lydia J Ansen-Wilson, Joshua L Everson, Dustin M Fink, Henry W Kietzman, Ruth Sullivan, Robert J Lipinski
Orofacial clefts (OFCs) of the lip and/or palate are among the most common human birth defects. Current treatment strategies focus on functional and cosmetic repair but even when this care is available, individuals born with OFCs are at high risk for persistent neurobehavioral problems. In addition to learning disabilities and reduced academic achievement, recent evidence associates OFCs with elevated risk for a constellation of psychiatric outcomes including anxiety disorders, autism spectrum disorder, and schizophrenia...
January 10, 2018: Translational Psychiatry
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