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https://read.qxmd.com/read/30763619/unravelling-protein-aggregation-as-an-ageing-related-process-or-a-neuropathological-response
#1
REVIEW
Diogo Trigo, André Nadais, Odete A B da Cruz E Silva
Protein aggregation is normally associated with amyloidosis, namely motor neurone, Alzheimer's, Parkinson's or prion diseases. However, recent results have unveiled a concept of gradual increase of protein aggregation associated with the ageing process, apparently not necessarily associated with pathological conditions. Given that protein aggregation is sufficient to activate stress-response and inflammation, impairing protein synthesis and quality control mechanisms, the former is assumed to negatively affect cellular metabolism and behaviour...
February 11, 2019: Ageing Research Reviews
https://read.qxmd.com/read/30761013/bestrophin-3-expression-in-a-subpopulation-of-astrocytes-in-the-neonatal-brain-after-hypoxic-ischemic-injury
#2
Veronika Golubinskaya, Regina Vontell, Veena Supramaniam, Josephine Wyatt-Ashmead, Helena Gustafsson, Carina Mallard, Holger Nilsson
Bestrophin-3, a potential candidate for a calcium-activated chloride channel, recently was suggested to have cell-protective functions. We studied the expression and alternative splicing of bestrophin-3 in neonatal mouse brain and after hypoxic-ischemic (HI) injury and in human neonatal brain samples. HI brain injury was induced in 9-day old mice by unilateral permanent common carotid artery occlusion in combination with exposure to 10% oxygen for 50 min. Endoplasmic reticulum stress was induced by thapsigargin treatment in primary culture of mouse brain astrocytes...
2019: Frontiers in Physiology
https://read.qxmd.com/read/30760829/polygenic-risk-for-neuropsychiatric-disease-and-vulnerability-to-abnormal-deep-grey-matter-development
#3
Harriet Cullen, Michelle L Krishnan, Saskia Selzam, Gareth Ball, Alessia Visconti, Alka Saxena, Serena J Counsell, Jo Hajnal, Gerome Breen, Robert Plomin, A David Edwards
Neuropsychiatric disease has polygenic determinants but is often precipitated by environmental pressures, including adverse perinatal events. However, the way in which genetic vulnerability and early-life adversity interact remains obscure. We hypothesised that the extreme environmental stress of prematurity would promote neuroanatomic abnormality in individuals genetically vulnerable to psychiatric disorders. In 194 unrelated infants (104 males, 90 females), born before 33 weeks of gestation (mean gestational age 29...
February 13, 2019: Scientific Reports
https://read.qxmd.com/read/30760285/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-protects-against-a%C3%AE-toxicity-via-attenuating-a%C3%AE-induced-endoplasmic-reticulum-stress
#4
Shengchun Xu, Zemin Di, Yufeng He, Runjie Wang, Yuyang Ma, Rui Sun, Jing Li, Tao Wang, Yujun Shen, Shengyun Fang, Lijie Feng, Yuxian Shen
BACKGROUND: Extracellular accumulation of amyloid β-peptide (Aβ) is one of pathological hallmarks of Alzheimer's disease (AD) and contributes to the neuronal loss. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) stress-inducible neurotrophic factor. Many groups, including ours, have proved that MANF rescues neuronal loss in several neurological disorders, such as Parkinson's disease and cerebral ischemia. However, whether MANF exerts its protective effect against Aβ neurotoxicity in AD remains unknown...
February 13, 2019: Journal of Neuroinflammation
https://read.qxmd.com/read/30759009/functional-studies-of-single-nucleotide-polymorphisms-suggest-heterogeneity-in-chronic-obstructive-pulmonary-disease-due-to-susceptibility-of-different-cell-types
#5
Yohannes Tesfaigzi, Hans Petersen, Bartolome Celli, Caroline Owen
Chronic obstructive pulmonary disease (COPD) is a syndrome that comprises several lung pathologies, but subphenotyping the various disease subtypes has not been successful. We found that a single-nucleotide polymorphism (SNP) within the proline-rich domain of transformation-related protein 53 (TP53) that modifies Pro72 to Arg is associated with twofold increased risk for chronic bronchitis in the Lovelace Smokers and COPDGene cohorts. This association is pronounced for those who report either wood smoke, dust, or fumes exposure...
December 2018: Annals of the American Thoracic Society
https://read.qxmd.com/read/30754072/nf-%C3%AE%C2%BAb-as-the-mediator-of-metformin-s-effect-on-aging-and-age-related-diseases
#6
REVIEW
G Kanigur Sultuybek, T Soydas, G Yenmis
Aging can be defined as the progressive failure of repair and maintenance systems with a consequent accumulation of cellular damage in nucleic acids, proteins, and lipids. These various types of damage promote aging by driving cellular senescence and apoptosis. NF-kB (nuclear factor-kappa B) pathway is one of the key mediators of aging and this pathway is activated by genotoxic, oxidative and inflammatory stress, and regulates expression of cytokines, growth factors, and genes that regulate apoptosis, cell cycle progression, and inflammation...
February 12, 2019: Clinical and Experimental Pharmacology & Physiology
https://read.qxmd.com/read/30747932/water-dispersible-astaxanthin-rich-nanopowder-preparation-oral-safety-and-antioxidant-activity-in-vivo
#7
Lei Guan, Junli Liu, Hanjieyu Yu, Huiqin Tian, Guanglu Wu, Boyu Liu, Ping Dong, Jing Li, Xingguo Liang
In this research, astaxanthin-rich nanopowder was prepared by nanoencapsulation and freeze-drying techniques with enhanced bioavailability and antioxidant activities. The nanopowder showed a maximum solubility of 230 mg mL-1 with an astaxanthin content as high as 2.9%. Compared with free astaxanthin, the astaxanthin-loaded nanopowder exhibited a more efficient antioxidant effect: an oral dose of 0.9 mg per kg BW significantly reduced the malondialdehyde and protein carbonyl contents, and increased the glutathione content as well as the superoxide dismutase activities in alcohol-induced acute hepatic injured mice, and maintained these oxidative stress indicators at a normal level for a longer period when treated with nanoencapsulated-astaxanthin than free astaxanthin...
February 12, 2019: Food & Function
https://read.qxmd.com/read/30745862/bidirectional-effects-of-pyrrolidine-dithiocarbamate-on-severe-acute-pancreatitis-in-a-rat-model
#8
Huan Yang, ShuCan Ma, Yu Guo, DongLai Cui, JinFeng Yao
Introduction: The mechanism by which intestinal mucosal barrier is damaged in severe acute pancreatitis (SAP)-associated impairment is not fully understood. Methods: We established an l-arginine-induced SAP rat model, pretreated with or without pyrrolidine dithiocarbamate (PDTC). Hematoxylin and eosin staining was performed to evaluate the pathological alterations. Western blotting was conducted to detect the expression of autophagy-related proteins. Oxidative stress was assessed by the levels of malondialdehyde and superoxide dismutase...
January 2019: Dose-response: a Publication of International Hormesis Society
https://read.qxmd.com/read/30745854/reactive-oxygen-species-related-noncoding-rnas-as-regulators-of-cardiovascular-diseases
#9
REVIEW
Yanhan Dong, Wenhua Xu, Cuiyun Liu, Peijun Liu, Peifeng Li, Kun Wang
Reactive oxygen species (ROS) are a class of reactive molecules that have been implicated in a variety of cardiovascular diseases, accompanied by disorder of multiple signaling events. As cardiomyocytes maintain abundant of mitochondria, which supply the major source of endogenous ROS, oxidative damage to mitochondria often drives apoptotic cell death and initiates cardiac pathology. In recent years, non-coding RNAs (ncRNAs) have received much attention to uncover their roles in regulating gene expression during those pathological events in the heart, such as myocardial infarction, cardiac hypertrophy, and heart failure...
2019: International Journal of Biological Sciences
https://read.qxmd.com/read/30745820/icariin-inhibits-endoplasmic-reticulum-stress-induced-neuronal-apoptosis-after-spinal-cord-injury-through-modulating-the-pi3k-akt-signaling-pathway
#10
Haotian Li, Xinran Zhang, Xi Qi, Xu Zhu, Liming Cheng
Endoplasmic reticulum (ER) stress-induced neuronal apoptosis is a crucial pathological process of spinal cord injury (SCI). In our previous study, icariin (ICA) showed neuroprotective effects in SCI. However, the relationships between ER stress and ICA in SCI are unclear yet. Therefore, whether ICA could ameliorate SCI via attenuating ER stress was investigated in vitro and in vivo . Adult mice were established SCI model and received vehicle solution or ICA by gavage once per day in vivo . The primary cultured cells were treated with or without thapsigargin (TG), ICA or LY294002 to induce ER stress in vitro ...
2019: International Journal of Biological Sciences
https://read.qxmd.com/read/30745416/rla8-a-new-and-highly-effective-quadruple-ppars-%C3%AE-%C3%AE-%C3%AE-and-gpr40-agonist-to-reverse-nonalcoholic-steatohepatitis-and-fibrosis
#11
Menghua Li, Wei Chen, Lili Wang, Jialin Sun, Lei Zhou, Yucong Shi, Chuhan Wang, Bohua Zhong, Weiguo Shi, Zhongwu Guo
Nonalcoholic fatty liver disease (NAFLD) is a very common chronic hepatic disease, with nonalcoholic steatohepatitis (NASH) as a major and severe subcategory that can lead to cirrhosis and hepatocellular carcinoma, thereby a high mortality rate. Currently, there has been no approved drug to treat NAFLD or NASH. The current study has presented RLA8, a novel and balanced quadruple agonist for hepatic lipid metabolism and inflammation-related peroxisome proliferator-activated receptors (PPARs)-α/γ/δ and G-protein-coupled receptor 40 (GPR40), as a NASH drug candidate...
February 11, 2019: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/30744115/post-stress-fructose-and-glucose-ingestion-exhibit-dissociable-behavioral-and-physiological-effects
#12
Michael A Conoscenti, Nicole M Williams, Lorraine P Turcotte, Thomas R Minor, Michael S Fanselow
An acute traumatic event can lead to lifelong changes in stress susceptibility and result in psychiatric disease such as Post-Traumatic Stress Disorder (PTSD). We have previously shown that access to a concentrated glucose solution for 24 hours beginning immediately after trauma decreased stress-related pathology in the learned helplessness model of PTSD and comorbid major depression. The current study sought to investigate the peripheral physiological effects of post-stress glucose consumption. We exposed 128 male Sprague-Dawley rats to inescapable and unpredictable 1-milliamp electric tail shocks or simple restraint in the learned helplessness procedure...
February 9, 2019: Nutrients
https://read.qxmd.com/read/30741672/thioredoxin-interacting-protein-txnip-associated-nlrp3-inflammasome-activation-in-human-alzheimer-s-disease-brain
#13
Lexiao Li, Saifudeen Ismael, Sanaz Nasoohi, Kazuko Sakata, Francesca-Fang Liao, Michael P McDonald, Tauheed Ishrat
Alzheimer's disease (AD) is the most common form of age-associated dementia characterized by amyloid-β plaques and neurofibrillary tangles. Recent studies have demonstrated that thioredoxin-interacting protein (TXNIP), an endogenous regulator of redox/glucose induced stress and inflammation, is now known to be upregulated in stroke, traumatic brain injury, diabetes and AD. We hypothesized that TXNIP overexpression sustains neurodegeneration through activation of the nucleotide binding and oligomerization domain-like receptor protein 3 in human AD brains...
February 6, 2019: Journal of Alzheimer's Disease: JAD
https://read.qxmd.com/read/30738887/sirt1-suppresses-p53-dependent-apoptosis-by-modulation-of-p21-in-osteoblast-like-mc3t3-e1-cells-exposed-to-fluoride
#14
Xiaolong Gu, Zhi Wang, Jian Gao, Dandan Han, Limei Zhang, Peng Chen, Guangjian Luo, Bo Han
Fluoride is very crucial for development of teeth and bones. Excessive fluoride, however, causes damage to teeth and bones resulting in serious public health problem. SIRT1 regulates physiological and pathological processes such as apoptosis and cell cycle. Although SIRT1 inhibits p53-mediated transactivation, how SIRT1 regulates p53 in fluorosis remains unclear. This study aims to investigate the involvement of SIRT1 in fluoride-induced cell cycle arrest and apoptosis in MC3T3-E1 cells and the underlying mechanism...
February 7, 2019: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://read.qxmd.com/read/30737170/impact-of-inhibition-of-the-autophagy-lysosomal-pathway-on-biomolecules-carbonylation-and-proteome-regulation-in-rat-cardiac-cells
#15
Giulia Coliva, Sofia Duarte, Dolores Pérez-Sala, Maria Fedorova
Cells employ multiple defence mechanisms to sustain a wide range of stress conditions associated with accumulation of modified self-biomolecules leading to lipo- and proteotoxicity. One of such mechanisms involves activation of the autophagy-lysosomal pathway for removal and degradation of modified lipids, proteins and even organelles. Biomolecules carbonylation, an irreversible oxidative modification, occurs in a variety of pathological conditions and is generally viewed as a marker of oxidative stress. Here, we used a model of rat primary cardiac cells to elucidate the role of autophagy-lysosomal pathway in the turnover of carbonylated biomolecules...
January 24, 2019: Redox Biology
https://read.qxmd.com/read/30737030/copper-ions-induce-dityrosine-linked-dimers-in-human-but-not-in-murine-islet-amyloid-polypeptide-iapp-amylin
#16
Xiaolin Dong, Teodor Svantesson, Sabrina B Sholts, Cecilia Wallin, Jüri Jarvet, Astrid Gräslund, Sebastian K T S Wärmländer
Dysregulation and aggregation of the peptide hormone IAPP (islet amyloid polypeptide, a.k.a. amylin) into soluble oligomers that appear to be cell-toxic is a known aspect of diabetes mellitus (DM) Type 2 pathology. IAPP aggregation is influenced by several factors including interactions with metal ions such as Cu(II). Because Cu(II) ions are redox-active they may contribute to metal-catalyzed formation of oxidative tyrosyl radicals, which can generate dityrosine cross-links. Here, we show that such a process, which involves Cu(II) ions bound to the IAPP peptide together with H2 O2 , can induce formation of large amounts of IAPP dimers connected by covalent dityrosine cross-links...
February 5, 2019: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/30735751/broccoli-sprout-beverage-is-safe-for-thyroid-hormonal-and-autoimmune-status-results-of-a-12-week-randomized-trial
#17
Dionysios V Chartoumpekis, Panos G Ziros, Jian-Guo Chen, John D Groopman, Thomas W Kensler, Gerasimos P Sykiotis
Sulforaphane is a redox-active natural product present in cruciferous vegetables like broccoli. Broccoli sprout-derived products are promising agents for the prevention of oxidative stress-related diseases, but some have long been suspected of thyroidal toxicity. Recent findings also raise the possibility that long-term exposure to sulforaphane, or to other natural substances or drugs that modulate the activity of the transcription factor Nrf2 (NFE2-related factor 2) may lead to thyroid dysfunction or thyroid autoimmune disease, questioning the safety of trials with sulforaphane-containing products...
February 5, 2019: Food and Chemical Toxicology
https://read.qxmd.com/read/30735502/toll-like-receptor-3-regulates-zika-virus-infection-and-associated-host-inflammatory-response-in-primary-human-astrocytes
#18
Chet Raj Ojha, Myosotys Rodriguez, Mohan Kumar Muthu Karuppan, Jessica Lapierre, Fatah Kashanchi, Nazira El-Hage
The connection between Zika virus (ZIKV) and neurodevelopmental defects is widely recognized, although the mechanisms underlying the infectivity and pathology in primary human glial cells are poorly understood. Here we show that three isolated strains of ZIKV, an African strain MR766 (Uganda) and two closely related Asian strains R103451 (Honduras) and PRVABC59 (Puerto Rico) productively infect primary human astrocytes, although Asian strains showed a higher infectivity rate and increased cell death when compared to the African strain...
2019: PloS One
https://read.qxmd.com/read/30733602/the-proteostasis-network-and-its-decline-in-ageing
#19
REVIEW
Mark S Hipp, Prasad Kasturi, F Ulrich Hartl
Ageing is a major risk factor for the development of many diseases, prominently including neurodegenerative disorders such as Alzheimer disease and Parkinson disease. A hallmark of many age-related diseases is the dysfunction in protein homeostasis (proteostasis), leading to the accumulation of protein aggregates. In healthy cells, a complex proteostasis network, comprising molecular chaperones and proteolytic machineries and their regulators, operates to ensure the maintenance of proteostasis. These factors coordinate protein synthesis with polypeptide folding, the conservation of protein conformation and protein degradation...
February 7, 2019: Nature Reviews. Molecular Cell Biology
https://read.qxmd.com/read/30725250/artemisia-amygdalina-upregulates-nrf2-and-protects-neurons-against-oxidative-stress-in-alzheimer-disease
#20
Nasreena Sajjad, Abubakar Wani, Ankita Sharma, Rohaya Ali, Sumaya Hassan, Rabia Hamid, Huma Habib, Bashir Ahmad Ganai
Alzheimer disease is a complex neurodegenerative disorder. It is the common form of dementia in elderly people. The etiology of this disease is multifactorial, pathologically it is accompanied with accumulation of amyloid beta and neurofibrillary tangles. Accumulation of amyloid beta and mitochondrial dysfunction leads to oxidative stress. In this study, neuroprotective effect of Artemisiaamygdalina against H2 O2 -induced death was studied in differentiated N2a and SH-SY5Ycells. Cells were treated with H2 O2 to induce toxicity which was attenuated by Artemisia amygdalina...
February 6, 2019: Cellular and Molecular Neurobiology
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