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Stress model for neurodegenerative disorders

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https://www.readbyqxmd.com/read/29136781/andrographolide-sulfonate-improves-alzheimer-associated-phenotypes-and-mitochondrial-dysfunction-in-app-ps1-transgenic-mice
#1
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/29129747/mitochondrial-sirt3-and-neurodegenerative-brain-disorders
#2
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/29129596/amyloid-toxicity-is-enhanced-after-pharmacological-or-genetic-invalidation-of-the-%C3%AF-1-receptor
#3
Tangui Maurice, Manon Strehaiano, Fanny Duhr, Nathalie Chevallier
The sigma-1 receptor (S1R) is a molecular chaperone which activity modulates several intracellular signals including calcium mobilization at mitochondria-associated endoplasmic reticulum membranes. S1R agonists are potent neuroprotectants against neurodegenerative insults and particularly in rodent models of Alzheimer's disease (AD). We here analyzed whether S1R inactivation modifies vulnerability to amyloid toxicity in AD models. Two strategies were used: (1) amyloid β[25-35] (Aβ25-35) peptide (1, 3, 9nmol) was injected intracerebroventricularly in mice treated repeatedly with the S1R antagonist NE-100 or in S1RKO mice, and (2) WT, APPSweInd, S1RKO, and APPSweInd/S1RKO mice were created and female littermates analyzed at 8 months of age...
November 9, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29104115/lowered-ipla2%C3%AE-activity-causes-increased-mitochondrial-lipid-peroxidation-and-mitochondrial-dysfunction-in-a-rotenone-induced-model-of-parkinson-s-disease
#4
Honglu Chao, Yinlong Liu, Xian Fu, Xiupeng Xu, Zhongyuan Bao, Chao Lin, Zheng Li, Yan Liu, Xiaoming Wang, Yongping You, Ning Liu, Jing Ji
iPLA2γ, calcium-independent phospholipase A2γ, discerningly hydrolyses glycerophospholipids to liberate free fatty acids. iPLA2γ-deficiency has been associated with abnormal mitochondrial function. More importantly, the iPLA2 family is causative proteins in mitochondrial neurodegenerative disorders such as parkinsonian disorders. However, the mechanisms by which iPLA2γ affects Parkinson's disease (PD) remain unknown. Mitochondrion stress has a key part in rotenone-induced dopaminergic neuronal degeneration...
November 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29089974/neuroprotective-effects-of-erythropoietin-on-neurodegenerative-and-ischemic-brain-diseases-the-role-of-erythropoietin-receptor
#5
REVIEW
Carolina Castillo Hernández, Carlos Felipe Burgos, Angela Hidalgo Gajardo, Tiare Silva-Grecchi, Javiera Gavilan, Jorge Roberto Toledo, Jorge Fuentealba
Erythropoietin (Epo) is a fundamental hormone in the regulation of hematopoiesis, and other secondary roles mediated by the binding of the hormone to its specific receptor (EpoR), which leads to an activation of key signaling pathways that induce an increase in cell differentiation, apoptosis control and neuroprotection. It has been suggested that their function depends on final conformation of glycosylations, related with affinity to the receptor and its half-life. The presence of EpoR has been reported in different tissues including central nervous system, where it has been demonstrated to exert a neuroprotective function against oxidative stress conditions, such as ischemic injury and neurodegenerative diseases...
September 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29081736/human-ipsc-derived-cerebellar-neurons-from-a-patient-with-ataxia-telangiectasia-reveal-disrupted-gene-regulatory-networks
#6
Sam P Nayler, Joseph E Powell, Darya P Vanichkina, Othmar Korn, Christine A Wells, Refik Kanjhan, Jian Sun, Ryan J Taft, Martin F Lavin, Ernst J Wolvetang
Ataxia-telangiectasia (A-T) is a rare genetic disorder caused by loss of function of the ataxia-telangiectasia-mutated kinase and is characterized by a predisposition to cancer, pulmonary disease, immune deficiency and progressive degeneration of the cerebellum. As animal models do not faithfully recapitulate the neurological aspects, it remains unclear whether cerebellar degeneration is a neurodevelopmental or neurodegenerative phenotype. To address the necessity for a human model, we first assessed a previously published protocol for the ability to generate cerebellar neuronal cells, finding it gave rise to a population of precursors highly enriched for markers of the early hindbrain such as EN1 and GBX2, and later more mature cerebellar markers including PTF1α, MATH1, HOXB4, ZIC3, PAX6, and TUJ1...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29073573/exposure-to-traffic-generated-air-pollutants-mediates-alterations-in-brain-microvascular-integrity-in-wildtype-mice-on-a-high-fat-diet
#7
Usa Suwannasual, JoAnn Lucero, Jacob D McDonald, Amie K Lund
Air pollution-exposure is associated with detrimental outcomes in the central nervous system (CNS) such as cerebrovascular disorders, including stroke, and neurodegenerative diseases. While the mechanisms of these CNS-related outcomes involved have not been fully elucidated, exposure to traffic-generated air pollutants has been associated with altered blood brain barrier (BBB) integrity and permeability. The current study investigated whether inhalation exposure to mixed vehicle emissions (MVE) alters cerebral microvascular integrity in healthy 3 mo old C57BL/6 mice, as well as whether exposure-mediated effects were exacerbated by a high-fat (HF) vs...
October 23, 2017: Environmental Research
https://www.readbyqxmd.com/read/29069955/shatavarin-iv-elicits-lifespan-extension-and-alleviates-parkinsonism-in-caenorhabditis-elegans
#8
Shachi Shuchi Smita, Shreesh Raj Sammi, Tulsankar S Laxman, Rabi S Bhatta, Rakesh Pandey
Shatavarin IV (SIV), a steroidal saponin is a major bioactive phytomolecule present in roots of Asparagus racemosus (Liliaceae) known for its anticancer activity. Age associated neurodegenerative Parkinson's disease (PD) is characterized by alpha-synuclein aggregation in dopaminergic neuron resulting in neurodegeneration. The invention of bioactive molecules that delay aging and age associated disorders endorses development of natural phytomolecule as a therapeutic agent for curing age related diseases. Therefore, present study for the first time explores the potential of SIV against aging and Parkinsonism utilizing Caenorhabditis elegans model system...
October 25, 2017: Free Radical Research
https://www.readbyqxmd.com/read/29068596/the-evaluation-of-the-changes-in-enzymatic-antioxidant-reserves-and-lipid-peroxidation-in-chosen-parts-of-the-brain-in-an-animal-model-of-parkinson-disease
#9
Ewa B Romuk, Wioletta Szczurek, Michał Oleś, Artur Gabrysiak, Marta Skowron, Przemysław Nowak, Ewa Birkner
BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The causes of Parkinson's disease are not fully understood; however, increasing evidence implicates oxidative stress. OBJECTIVES: The study was aimed at assessing the nature of the changes in the oxidation-antioxidant balance in the cerebral cortex, striatum, hippocampus, thalamus, and cerebellum in a rat model of Parkinson's disease (PD)...
September 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29066277/therapeutic-application-of-apoptosis-signal-regulating-kinase-1-inhibitors
#10
REVIEW
Takao Fujisawa
Apoptosis signal-regulating kinase 1 (ASK1) is a member of the stress-activated mitogen-activated protein kinase kinase kinase (MAP3K) family. ASK1 is an attractive drug target, owing to its essential role in a wide variety of human diseases including neurodegenerative disorders, inflammatory diseases and cancer. Recent studies have suggested that pharmacological manipulations using small molecule ASK1 inhibitors may be beneficial in experimental human disease models. In this review, we highlight the current understanding of ASK1 inhibitors as a potential therapy for human diseases...
October 16, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29061563/rescue-of-atxn3-neuronal-toxicity-in-c-elegans-by-chemical-modification-of-er-stress
#11
Yasmin Fardghassemi, Arnaud Tauffenberger, Sarah Gosselin, J Alex Parker
Background: Polyglutamine expansion diseases are a group of hereditary neurodegenerative disorders that develop when a CAG repeat in the causative genes are unstably expanded above a certain threshold. The expansion of trinucleotide CAG repeats cause hereditary adult-onset neurodegenerative disorders such as Huntington's disease, dentatorubral-pallidoluysian atrophy, spinobulbar muscular atrophy and multiple forms of spinocerebellar ataxia (SCA). The most common dominantly inherited spinocerebellar ataxia is the type 3 (SCA3) also known as Machado-Joseph disease (MJD), is an autosomal dominant, progressive neurological disorder...
October 23, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29048427/hdac6-inhibition-by-tubastatin-a-is-protective-against-oxidative-stress-in-a-photoreceptor-cell-line-and-restores-visual-function-in-a-zebrafish-model-of-inherited-blindness
#12
Janina Leyk, Conor Daly, Ulrike Janssen-Bienhold, Breandán N Kennedy, Christiane Richter-Landsberg
Retinal diseases, such as hereditary retinitis pigmentosa and age-related macular degeneration, are characterized by the progressive loss of photoreceptors. Histone deacetylase 6 (HDAC6) is considered as a stress surveillance factor and a potential target for neuroprotection and regeneration. Overexpression of HDAC6 has been connected to neurodegenerative disorders, and its suppression may provide protection. Here we show that HDAC6 is constitutively present in the mouse retina, and in the cone-like mouse cell line 661W...
August 31, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29036434/novel-mechanisms-of-eif2b-action-and-regulation-by-eif2%C3%AE-phosphorylation
#13
Andrew M Bogorad, Kai Ying Lin, Assen Marintchev
Eukaryotic translation initiation factor 2 (eIF2) is a heterotrimeric GTPase, which plays a critical role in protein synthesis regulation. eIF2-GTP binds Met-tRNAi to form the eIF2-GTP•Met-tRNAi ternary complex (TC), which is recruited to the 40S ribosomal subunit. Following GTP hydrolysis, eIF2-GDP is recycled back to TC by its guanine nucleotide exchange factor (GEF), eIF2B. Phosphorylation of the eIF2α subunit in response to various cellular stresses converts eIF2 into a competitive inhibitor of eIF2B, which triggers the integrated stress response (ISR)...
September 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29030433/dysregulation-of-the-mitochondrial-unfolded-protein-response-induces-non-apoptotic-dopaminergic-neurodegeneration-in-c-elegans-models-of-parkinson-s-disease
#14
Bryan A Martinez, Daniel A Petersen, Anthony L Gaeta, Samuel P Stanley, Guy A Caldwell, Kim A Caldwell
Due to environmental insult or innate genetic deficiency, protein folding environments of the mitochondrial matrix are prone to dysregulation, prompting the activation of a specific organellar stress-response mechanism, the mitochondrial unfolded protein response (UPR(MT)). In Caenorhabditis elegans, mitochondrial damage leads to nuclear translocation of the ATFS-1 transcription factor to activate the UPR(MT) After short-term acute stress has been mitigated, the UPR(MT) is eventually suppressed to restore homeostasis to C...
November 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29027929/procyanidin-b2-protects-neurons-from-oxidative-nitrosative-and-excitotoxic-stress
#15
Taylor C Sutcliffe, Aimee N Winter, Noelle C Punessen, Daniel A Linseman
The aberrant generation of oxygen and nitrogen free radicals can cause severe damage to key cellular components, resulting in cell apoptosis. Similarly, excitotoxicity leads to protease activation and mitochondrial dysfunction, which subsequently causes cell death. Each of these factors play critical roles in the neuronal cell death underlying various neurodegenerative diseases. Procyanidin B2 (PB2) is a naturally occurring polyphenolic compound found in high concentrations in cocoa, apples, and grapes. Here, we examine the neuroprotective effects of PB2 in primary cultures of rat cerebellar granule neurons (CGNs) exposed to various stressors...
October 13, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29024164/understanding-role-of-steroids-in-typical-and-atypical-brain-development-advantages-of-using-a-brain-in-a-dish-approach
#16
REVIEW
Dwaipayan Adhya, Emily Annuario, Madeline A Lancaster, Jack Price, Simon Baron-Cohen, Deepak P Srivastava
Steroids have an important role in growth, development, sexual differentiation and reproduction. All four classes of steroids, androgens, estrogens, progestogens and glucocorticoids, have varying effects on the brain. Androgens and estrogens are involved in the sexual differentiation of the brain, and also influence cognition. Progestogens such as progesterone and its metabolites have been shown to be involved in neuroprotection, although their protective effects are timing dependent. Glucocorticoids are linked with stress and memory performance, also in a dose- and time-dependent manner...
October 12, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28985333/nonhuman-primate-models-of-neurodegenerative-disorders
#17
Marina E Emborg
Alzheimer's (AD), Huntington's (HD), and Parkinson's (PD) disease are age-related neurodegenerative disorders characterized by progressive neuronal cell death. Although each disease has particular pathologies and symptoms, accumulated evidence points to similar mechanisms of neurodegeneration, including inflammation, oxidative stress, and protein aggregation. A significant body of research is ongoing to understand how these pathways affect each other and what ultimately triggers the onset of the disease. Experiments in nonhuman primates (NHPs) account for only 5% of all research in animals...
August 10, 2017: ILAR Journal
https://www.readbyqxmd.com/read/28984582/multiple-system-atrophy-an%C3%A2-oligodendroglioneural-synucleinopathy
#18
Kurt A Jellinger
Multiple system atrophy (MSA) is an orphan, fatal, adult-onset neurodegenerative disorder of uncertain etiology that is clinically characterized by various combinations of parkinsonism, cerebellar, autonomic, and motor dysfunction. MSA is an α-synucleinopathy with specific glioneuronal degeneration involving striatonigral, olivopontocerebellar, and autonomic nervous systems but also other parts of the central and peripheral nervous systems. The major clinical variants correlate with the morphologic phenotypes of striatonigral degeneration (MSA-P) and olivopontocerebellar atrophy (MSA-C)...
September 26, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28973191/pyroglutamate-amyloid-%C3%AE-peptide-expression-in-drosophila-leads-to-caspase-dependent-and-endoplasmic-reticulum-stress-related-progressive-neurodegeneration
#19
Leo Tsuda, Omata Yasuhiro, Yasutoyo Yamasaki, Ryunosuke Minami, Young-Mi Lim
Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly. During the progression of AD, massive neuronal degeneration occurs in the late stage of the disease; however, the molecular mechanisms responsible for this neuronal loss remain unknown. AßpE3-42 (an N-terminal-truncated amyloid-ß peptide that begins with pyroglutamate at the third position) is produced during late-stage AD.It also aggregates more rapidly in vitro and exhibits greater toxicity in neurons than full-length Aß1-42...
September 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28956338/the-role-of-phosphodiesterase-2-in-psychiatric-and-neurodegenerative-disorders
#20
Chong Zhang, Lindsay M Lueptow, Han-Ting Zhang, James M O'Donnell, Ying Xu
Cyclic nucleotide PDEs are a super-family of enzymes responsible for regulating intracellular levels of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Through their catalysis, PDEs are able to exert tight regulation over these important intracellular signaling cascades. Previously, PDEs have been implicated in learning and memory, as well as in mood disorders, such as anxiety and depression. PDE2 is of special interest due to its high level of expression in the forebrain, specifically in the isocortex, entorhinal cortex, striatum, hippocampus, amygdala, and medial habenula...
2017: Advances in Neurobiology
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