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https://www.readbyqxmd.com/read/29150992/accelerated-aging-and-aging-process-in-the-brain
#1
Nickolay K Isaev, Elisaveta E Genrikhs, Maria V Oborina, Elena V Stelmashook
One of the approaches to the research of the problem of aging is the study of genetic pathologies leading to accelerated aging, such as the Hutchinson-Gilford progeria syndrome, Werner syndrome, and Down syndrome. Probably, this approach can be used in an attempt to understand the neuronal mechanisms underlying normal and pathological brain aging. The analysis of the current state of scientific knowledge about these pathologies shows that in the Hutchinson-Gilford progeria and Werner syndrome, the rate of brain aging is significantly lower than the rate of whole body aging, whereas in Down syndrome, the brain ages faster than other organs due to amyloid-beta accumulation and chronic oxidative stress in the brain tissue...
November 18, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29136781/andrographolide-sulfonate-improves-alzheimer-associated-phenotypes-and-mitochondrial-dysfunction-in-app-ps1-transgenic-mice
#2
Ji Geng, Wen Liu, Yuyun Xiong, Hongqun Ding, Chunhong Jiang, Xiaoling Yang, Xiang Li, Ahmed Elgehama, Yang Sun, Qiang Xu, Wenjie Guo, Jing Gao
Alzheimer's disease is a neurodegenerative disorder with Amyloid-β plaques onset, synaptic damage, and cognitive decline. Aβ deposits cause pathological events including oxidative stress, mitochondrial dysfunction, and neuron death. In this study, APPswe/PSENΔ9 double transgenic mice model was used to imitate Alzheimer's disease and the effect and possible mechanism of Andrographolide sulfonate were examined. Andrographolide sulfonate was given to the mice for 7 months before the onset of Aβ plaque. Spatial memory test showed that Andrographolide sulfonate treatment prevented cognitive decline...
November 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29134778/the-axonal-endoplasmic-reticulum-one-organelle-many-functions-in-development-maintenance-and-plasticity
#3
REVIEW
Alejandro Luarte, Víctor Hugo Cornejo, Francisca Bertin, Javiera Gallardo, Andrés Couve
The endoplasmic reticulum (ER) is highly conserved in eukaryotes and neurons. Indeed, the localization of the organelle in axons has been known for nearly half a century. However, the relevance the axonal ER is only beginning to emerge. In this review we discuss the structure of the ER in axons, examining the role of ER-shaping proteins and highlighting reticulons. We analyze the multiple functions of the ER and their potential contribution to axonal physiology. First we examine the emerging roles of the axonal ER in lipid synthesis, protein translation, processing, quality control and secretory trafficking of transmembrane proteins...
November 14, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/29133339/decreased-ceramide-underlies-mitochondrial-dysfunction-in-charcot-marie-tooth-2f
#4
Nicholas U Schwartz, Ryan W Linzer, Jean-Philip Truman, Mikhail Gurevich, Yusuf A Hannun, Can E Senkal, Lina M Obeid
Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurologic disorder, but its molecular mechanisms remain unclear. One variant of CMT, 2F, is characterized by mutations in heat shock protein 27 (Hsp27). As bioactive sphingolipids have been implicated in neurodegenerative diseases, we sought to determine if their dysregulation is involved in CMT. Here, we show that Hsp27 knockout mice demonstrated decreases in ceramide in peripheral nerve tissue and that the disease-associated Hsp27 S135F mutant demonstrated decreases in mitochondrial ceramide...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29130578/sirt3-deregulation-is-linked-to-mitochondrial-dysfunction-in-alzheimer-s-disease
#5
Junghee Lee, Yunha Kim, Tian Liu, Yu Jin Hwang, Seung Jae Hyeon, Hyeonjoo Im, Kyungeun Lee, Victor E Alvarez, Ann C McKee, Soo-Jong Um, Manwook Hur, Inhee Mook-Jung, Neil W Kowall, Hoon Ryu
Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. Sirtuins (SIRT, silent mating type information regulation 2 homolog in yeast) are NAD-dependent histone deacetylases involved in aging and longevity. The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD...
November 11, 2017: Aging Cell
https://www.readbyqxmd.com/read/29129747/mitochondrial-sirt3-and-neurodegenerative-brain-disorders
#6
REVIEW
Anamika, Archita Khanna, Papia Acharjee, Arup Acharjee, Surendra Kumar Trigun
Sirtuins are highly conserved NAD(+) dependent class III histone deacetylases and catalyze deacetylation and ADP ribosylation of a number of non-histone proteins. Since, they require NAD(+) for their activity, the cellular level of Sirtuins represents redox status of the cells and thereby serves as bona fide metabolic stress sensors. Out of seven homologues of Sirtuins identified in mammals, SIRT3, 4 & 5 have been found to be localized and active in mitochondria. During recent past, clusters of protein substrates for SIRT3 have been identified in mitochondria and thereby advocating SIRT3 as the main mitochondrial Sirtuin which could be involved in protecting stress induced mitochondrial integrity and energy metabolism...
November 9, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29129679/pecularities-of-the-structure-of-glycogen-as-an-indicator-of-the-functional-state-of-mauthner-neurons-in-fish-perc%C3%B1-ottus-glehni-during-wintering
#7
Irina M Santalova, Rita Ya Gordon, Irina B Mikheeva, Sergei S Khutsian, Eugene I Maevsky
Mauthner neurons (MN)*, specific multifunctional neurons of fish, are a unique object for investigating the adaptive potentialities of the cell. The goal of the work was to study the structure of MN of fish Percсottus glehni during wintering under the conditions of hypothermia and deficit of oxygen and energy substrates. It was shown using a light microscope that the volume of the somatic moiety of neurons changes slightly at the beginning of wintering and is significantly reduced by the termination of wintering...
November 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29129468/inhibition-of-rac1-ameliorates-neuronal-oxidative-stress-damage-via-reducing-bcl-2-rac1-complex-formation-in-mitochondria-through-pi3k-akt-mtor-pathway
#8
Yundan Pan, Na Wang, Pingping Xia, E Wang, Qulian Guo, Zhi Ye
Although the neuroprotective effects of Rac1 inhibition have been reported in various cerebral ischemic models, the molecular mechanisms of action have not yet been fully elucidated. In this study, we investigated whether the inhibition of Rac1 provided neuroprotection in a diabetic rat model of focal cerebral ischemia and hyperglycemia-exposed PC-12 cells. Intracerebroventricular administration of lentivirus expressing the Rac1 small hairpin RNA (shRNA) and specific Rac1 inhibitor NSC23766 not only decreased the infarct volumes and improved neurologic deficits with a correlated significant activation of mitochondrial DNA specific proteins, such as OGG1 and POLG, but also elevated Bcl-2 S70 phosphorylation in mitochondria...
November 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29128415/the-p38-mitogen-activated-protein-kinase-regulates-%C3%AE-amyloid-protein-internalization-through-the-%C3%AE-7-nicotinic-acetylcholine-receptor-in-mouse-brain
#9
Kai-Ge Ma, Jia Lv, Wei-Na Yang, Ke-Wei Chang, Xiao-Dan Hu, Li-Li Shi, Wan-Ying Zhai, Hang-Fan Zong, Yi-Hua Qian
Alzheimer's disease (AD) is one of the most devastating neurodegenerative disorders. Intracellular β-amyloid protein (Aβ) is an early event in AD. It induces the formation of amyloid plaques and neuron damage. The α7 nicotinic acetylcholine receptor (α7nAChR) has been suggested to play an important role in Aβ caused cognition. It has high affinity with Aβ and could mediate Aβ internalization in vitro. However, whether in mouse brain the p38 MAPK signaling pathway is involved in the regulation of the α7nAChR mediated Aβ internalization and their role in mitochondria remains little known...
November 9, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29123128/pink1-mediated-phosphorylation-of-letm1-regulates-mitochondrial-calcium-transport-and-protects-neurons-against-mitochondrial-stress
#10
En Huang, Dianbo Qu, Tianwen Huang, Nicoletta Rizzi, Wassamon Boonying, Dorothy Krolak, Paolo Ciana, John Woulfe, Christine Klein, Ruth S Slack, Daniel Figeys, David S Park
Mutations in PTEN-induced kinase 1 (PINK1) result in a recessive familial form of Parkinson's disease (PD). PINK1 loss is associated with mitochondrial Ca(2+) mishandling, mitochondrial dysfunction, as well as increased neuronal vulnerability. Here we demonstrate that PINK1 directly interacts with and phosphorylates LETM1 at Thr192 in vitro. Phosphorylated LETM1 or the phospho-mimetic LETM1-T192E increase calcium release in artificial liposomes and facilitates calcium transport in intact mitochondria. Expression of LETM1-T192E but not LETM1-wild type (WT) rescues mitochondrial calcium mishandling in PINK1-deficient neurons...
November 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/29119535/mitochondria-bound-hexokinase-mt-hk-activity-differ-in-cortical-and-hypothalamic-synaptosomes-differential-role-of-mt-hk-in-h2o2-depuration
#11
João Paulo Cavalcanti-de-Albuquerque, Eduardo de Souza Ferreira, Denise Pires de Carvalho, Antonio Galina
Glucose and oxygen are vital for the brain, as these molecules provide energy and metabolic intermediates that are necessary for cell function. The glycolysis pathway and mitochondria play a pivotal role in cell energy metabolism, which is closely related to reactive oxygen species (ROS) production. Hexokinase (HK) is a key enzyme involved in glucose metabolism that modulates the level of brain mitochondrial ROS by recycling ADP for oxidative phosphorylation (OxPhos). Here, we hypothesize that the control of mitochondrial metabolism by hexokinase differs in distinct areas of the brain, such as the cortex and hypothalamus, in which ROS might function as signaling molecules...
November 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29117569/ros-control-mitochondrial-motility-through-p38-and-the-motor-adaptor-miro-trak
#12
Valentina Debattisti, Akos A Gerencser, Masao Saotome, Sudipto Das, György Hajnóczky
Mitochondrial distribution and motility are recognized as central to many cellular functions, but their regulation by signaling mechanisms remains to be elucidated. Here, we report that reactive oxygen species (ROS), either derived from an extracellular source or intracellularly generated, control mitochondrial distribution and function by dose-dependently, specifically, and reversibly decreasing mitochondrial motility in both rat hippocampal primary cultured neurons and cell lines. ROS decrease motility independently of cytoplasmic [Ca(2+)], mitochondrial membrane potential, or permeability transition pore opening, known effectors of oxidative stress...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29117544/glial-cell-evolution-the-origins-of-a-lipid-store
#13
Klaus-Armin Nave, Iva D Tzvetanova, Stefanie Schirmeier
In Drosophila, neuronal mitochondria that lack OXPHOS generate ROS-protective fatty acids and lipid droplets in associated glia. In this issue, Liu et al. (2017) demonstrate that neuronal lipid synthesis is driven by the glial lactate shuttle. This lipoprotein-dependent deposition of lipids may be at the origin of glial specializations evolving in vertebrates.
November 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29111377/mass-spectrometry-analyses-of-normal-and-polyglutamine-expanded-ataxin-3-reveal-novel-interaction-partners-involved-in-mitochondrial-function
#14
Line V Kristensen, Felix S Oppermann, Matthias J Rauen, Karina Fog, Thorsten Schmidt, Jana Schmidt, Tina Harmuth, Rasmus Hartmann-Petersen, Kenneth Thirstrup
Deubiquitinating enzymes (DUBs) play important roles in a variety of cellular processes, including regulation of protein homeostasis. The DUB ataxin-3 is an enzyme implicated in protein quality control mechanisms. In the neurodegenerative disease spinocerebellar ataxia type 3 (SCA3), ataxin-3 contains an expanded polyglutamine (polyQ) stretch that leads to aggregation of the protein and neuronal dysfunction. Increasing the understanding of ataxin-3 protein interaction partners could help to elucidate disease mechanisms...
October 27, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29110115/dnm1l-variant-alters-baseline-mitochondrial-function-and-response-to-stress-in-a-patient-with-severe-neurological-dysfunction
#15
Kaley A Hogarth, Sheila R Costford, Grace Yoon, Neal Sondheimer, Jason T Maynes
Mitochondria play vital roles in brain development and neuronal activity, and mitochondrial dynamics (fission and fusion) maintain organelle function through the removal of damaged components. Dynamin-like protein-1 (DRP-1), encoded by DNM1L, is an evolutionarily conserved GTPase that mediates mitochondrial fission by surrounding the scission site in concentric ring-like structures via self-oligomerization, followed by GTPase-dependant constriction. Here, we describe the clinical characteristics and cellular phenotype of a patient with severe neurological dysfunction, possessing a homozygous DNM1L variant c...
November 6, 2017: Biochemical Genetics
https://www.readbyqxmd.com/read/29107957/febuxostat-ameliorates-secondary-progressive-experimental-autoimmune-encephalomyelitis-by-restoring-mitochondrial-energy-production-in-a-got2-dependent-manner
#16
Josephe A Honorat, Yuji Nakatsuji, Mikito Shimizu, Makoto Kinoshita, Hisae Sumi-Akamaru, Tsutomu Sasaki, Kazushiro Takata, Toru Koda, Akiko Namba, Kazuya Yamashita, Eri Sanda, Manabu Sakaguchi, Atsushi Kumanogoh, Takashi Shirakura, Mizuho Tamura, Saburo Sakoda, Hideki Mochizuki, Tatsusada Okuno
Oxidative stress and mitochondrial dysfunction are important determinants of neurodegeneration in secondary progressive multiple sclerosis (SPMS). We previously showed that febuxostat, a xanthine oxidase inhibitor, ameliorated both relapsing-remitting and secondary progressive experimental autoimmune encephalomyelitis (EAE) by preventing neurodegeneration in mice. In this study, we investigated how febuxostat protects neuron in secondary progressive EAE. A DNA microarray analysis revealed that febuxostat treatment increased the CNS expression of several mitochondria-related genes in EAE mice, most notably including GOT2, which encodes glutamate oxaloacetate transaminase 2 (GOT2)...
2017: PloS One
https://www.readbyqxmd.com/read/29107612/the-protective-effect-of-2-2-benzonfu-ranyl-2-imidazoline-against-oxygen-glucose-deprivation-in-cultured-rat-cortical-astrocytes
#17
Jisha Tian, Rui Chen, Lan Hu, Linglei Zhang, Jiaou Chen, Yungang Cao, Xiaoling Guo, Longqing Wang, Zhao Han
Astrocytes play a pivotal role in neuronal survival in the setting of post-ischemic brain inflammation, but the astrocyte-derived mediators of ischemic brain injury remain to be defined. 2-(2-Benzofu-ranyl)-2-imidazoline (2-BFI) is a newly discovered ligand for high-affinity imidazoline I2 receptors (I2Rs) mainly located on the mitochondrial outer membrane in astrocytes. We previously reported that in a rat model of cerebral ischemia-reperfusion injury, 2-BFI limits infarct volume, reduces neurological impairment scores, and inhibits neuronal apoptosis in the ischemic penumbra...
October 28, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29106903/crocin-attenuates-acute-hypobaric-hypoxia-induced-cognitive-deficits-of-rats
#18
Xiao-Yan Zhang, Xian-Jun Zhang, Jin Xv, Wei Jia, Xiao-Yan Pu, Hai-Yan Wang, Hong Liang, Zhuoma-Lamao, Dian-Xiang Lu
This study investigated whether crocin exerted neuroprotective effects against acute hypobaric hypoxia at high altitude in vivo and determined the underlying mechanisms. Male Sprague-Dawley rats were randomly assigned to a normoxic group,a hypoxic group, and three crocin groups at three different doses. The rats were transferred from 50m to 4200m for 3 days after treatment with crocin for 3 days. The learning and memory of the rat were evaluated with the Morris water maze test. Transmission electron microscope (TEM) was used to analyze the changes in the ultrastructure of hippocampal neurons...
October 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29104120/methylmercury-exposure-causes-a-persistent-inhibition-of-myogenin-expression-and-c2c12-myoblast-differentiation
#19
Lisa M Prince, Matthew D Rand
Methylmercury (MeHg) is a ubiquitous environmental toxicant, best known for its selective targeting of the developing nervous system. MeHg exposure has been shown to cause motor deficits such as impaired gait and coordination, muscle weakness, and muscle atrophy, which have been associated with disruption of motor neurons. However, recent studies have suggested that muscle may also be a target of MeHg toxicity, both in the context of developmental myogenic events and of low-level chronic exposures affecting muscle wasting in aging...
November 2, 2017: Toxicology
https://www.readbyqxmd.com/read/29103101/ischemic-preconditioning-protects-astrocytes-against-oxygen-glucose-deprivation-via-the-nuclear-erythroid-2-related-factor-2-pathway
#20
Srinivasan V Narayanan, Kunjan R Dave, Miguel A Perez-Pinzon
Induction of ischemic preconditioning (IPC) represents a potential therapy against cerebral ischemia by activation of adaptive pathways and modulation of mitochondria to induce ischemic tolerance to various cells and tissues. Mitochondrial dysfunction has been ascribed to contribute to numerous neurodegenerative conditions and cerebral ischemia. Nuclear erythroid 2-related factor 2 (Nrf2) is a transcription factor that has traditionally been involved in upregulating cellular antioxidant systems to combat oxidative stress in the brain; however, the association of Nrf2 with mitochondria in the brain remains unclear...
November 4, 2017: Translational Stroke Research
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