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Neurodegeneration

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https://www.readbyqxmd.com/read/28937955/military-blast-injury-and-chronic-neurodegeneration-research-presentations-from-the-2015-international-state-of-the-science-meeting
#1
Denes Agoston, Peethambaran Arun, Patrick Bellgowan, Steven Broglio, Robert Cantu, David Cook, Uade Olaghere da Silva, Dara Dickstein, Gregory Elder, Elizabeth Fudge, Sam Gandy, Jessica Gill, John F Glenn, Raj K Gupta, Sidney Hinds, Stuart Hoffman, Theresa Lattimore, Alexander Lin, Kun Ping Lu, Joseph Maroon, David Okonkwo, Daniel Perl, Meghan Robinson, Charles Rosen, Douglas Smith
Blast-related traumatic brain injury (TBI) is a signature injury of recent military conflicts, leading to increased Department of Defense (DoD) interest in its potential long-term effects, such as chronic traumatic encephalopathy (CTE). The DoD Blast Injury Research Program Coordinating Office convened the 2015 International State-of-the-Science Meeting to discuss the existing evidence regarding a causal relationship between TBI and CTE. Over the course of the meeting, experts across government, academia, and the sports community presented cutting edge research on the unique pathological characteristics of blast-related TBI, blast-related neurodegenerative mechanisms, risk factors for CTE, potential biomarkers for CTE, and treatment strategies for chronic neurodegeneration...
September 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28937602/licochalcone-a-prevents-the-loss-of-dopaminergic-neurons-by-inhibiting-microglial-activation-in-lipopolysaccharide-lps-induced-parkinson-s-disease-models
#2
Bingxu Huang, Juxiong Liu, Chen Ju, Dongxue Yang, Guangxin Chen, Shiyao Xu, Yalong Zeng, Xuan Yan, Wei Wang, Dianfeng Liu, Shoupeng Fu
The neuroprotective effects of Licochalcone A (Lico.A), a flavonoid isolated from the herb licorice, in Parkinson's disease (PD) have not been elucidated. The prominent pathological feature of PD is the loss of dopaminergic neurons. The crucial role of neuroinflammation induced by activated microglia in dopaminergic neurodegeneration has been validated. In this study, we explore the therapeutic effects of Lico.A in lipopolysaccharide (LPS)-induced PD models in vivo and in vitro. We find that Lico.A significantly inhibits LPS-stimulated production of pro-inflammatory mediators and microglial activation by blocking the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and nuclear factor κB (NF-κB) p65 in BV-2 cells...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28936789/toxic-synergism-between-quinolinic-acid-and-glutaric-acid-in-neuronal-cells-is-mediated-by-oxidative-stress-insights-to-a-new-toxic-model
#3
Paula Pierozan, Ana Laura Colín-González, Helena Biasibetti, Janaina Camacho da Silva, Angela Wyse, Moacir Wajner, Abel Santamaria
It has been shown that synergistic toxic effects of quinolinic acid (QUIN) and glutaric acid (GA), both in isolated nerve endings and in vivo conditions, suggest the contribution of these metabolites to neurodegeneration. However, this synergism still requires a detailed characterization of the mechanisms involved in cell damage during its occurrence. In this study, the effects of subtoxic concentrations of QUIN and/or GA were tested in neuronal cultures, co-cultures (neuronal cells + astrocytes), and mixed cultures (neuronal cells + astrocytes + microglia) from rat cortex and striatum...
September 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28936366/constitutive-and-stress-induced-expression-of-ccl5-machinery-in-rodent-retina
#4
D'Anne S Duncan, William M McLaughlin, Noah Vasilakes, Franklin D Echevarria, Cathryn R Formichella, Rebecca M Sappington
Signaling by inflammatory cytokines and chemokines is associated with neurodegeneration in disease and injury. Here we examined expression of the β-chemokine CCL5 and its receptors in the mouse retina and evaluated its relevance in glaucoma, a common optic neuropathy associated with sensitivity to intraocular pressure (IOP). Using quantitative PCR, fluorescent in situ hybridization, immunohistochemistry and quantitative image analysis, we found CCL5 mRNA and protein was constitutively expressed in the inner retina and synaptic layers...
June 2017: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/28936163/quercetin-declines-apoptosis-ameliorates-mitochondrial-function-and-improves-retinal-ganglion-cell-survival-and-function-in-in-vivo-model-of-glaucoma-in-rat-and-retinal-ganglion-cell-culture-in-vitro
#5
Feng-Juan Gao, Sheng-Hai Zhang, Ping Xu, Bo-Qi Yang, Rong Zhang, Yun Cheng, Xu-Jiao Zhou, Wan-Jing Huang, Min Wang, Jun-Yi Chen, Xing-Huai Sun, Ji-Hong Wu
Glaucoma is a progressive neuropathy characterized by the loss of retinal ganglion cells (RGCs). Strategies that delay or halt RGC loss have been recognized as potentially beneficial for rescuing vision in glaucoma patients. Quercetin (Qcn) is a natural and important dietary flavonoid compound, widely distributed in fruits and vegetables. Mounting evidence suggests that Qcn has numerous neuroprotective effects. However, whether Qcn exerts neuroprotective effects on RGC in glaucoma is poorly understood. In this study, we investigated the protective effect of Qcn against RGC damage in a rat chronic ocular hypertension (COHT) model invivo and hypoxia-induced primary cultured RGC damage in vitro, and we further explored the underlying neuroprotective mechanisms...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28935930/characterization-of-soft-amyloid-cores-in-human-prion-like-proteins
#6
Cristina Batlle, Natalia Sanchez de Groot, Valentin Iglesias, Susanna Navarro, Salvador Ventura
Prion-like behaviour is attracting much attention due to the growing evidences that amyloid-like self-assembly may reach beyond neurodegeneration and be a conserved functional mechanism. The best characterized functional prions correspond to a subset of yeast proteins involved in translation or transcription. Their conformational promiscuity is encoded in Prion Forming Domains (PFDs), usually long and intrinsically disordered protein segments of low complexity. The compositional bias of these regions seems to be important for the transition between soluble and amyloid-like states...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935914/neurodegenerative-disease-dlk-zips-across-neurodegeneration
#7
M Teresa Villanueva
No abstract text is available yet for this article.
September 22, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28935901/a-brain-targeting-lipidated-peptide-for-neutralizing-rna-mediated-toxicity-in-polyglutamine-diseases
#8
Qian Zhang, Mengbi Yang, Kasper K Sørensen, Charlotte S Madsen, Josephine T Boesen, Ying An, Shao Hong Peng, Yuming Wei, Qianwen Wang, Knud J Jensen, Zhong Zuo, Ho Yin Edwin Chan, Jacky Chi Ki Ngo
Polyglutamine (PolyQ) diseases are progressive neurodegenerative disorders caused by both protein- and RNA-mediated toxicities. We previously showed that a peptidyl inhibitor, P3, which binds directly to expanded CAG RNA can inhibit RNA-induced nucleolar stress and suppress RNA-induced neurotoxicity. Here we report a N-acetylated and C-amidated derivative of P3, P3V8, that showed a more than 20-fold increase in its affinity for expanded CAG RNA. The P3V8 peptide also more potently alleviated expanded RNA-induced cytotoxicity in vitro, and suppressed polyQ neurodegeneration in Drosophila with no observed toxic effects...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28934963/metabolic-status-of-csf-distinguishes-rats-with-tauopathy-from-controls
#9
Radana Karlíková, Kateřina Mičová, Lukáš Najdekr, Alžběta Gardlo, Tomáš Adam, Petra Majerová, David Friedecký, Andrej Kováč
BACKGROUND: Tauopathies represent heterogeneous groups of neurodegenerative diseases that are characterised by abnormal deposition of the microtubule-associated protein tau. Alzheimer's disease is the most prevalent tauopathy, affecting more than 35 million people worldwide. In this study we investigated changes in metabolic pathways associated with tau-induced neurodegeneration. METHODS: Cerebrospinal fluid (CSF), plasma and brain tissue were collected from a transgenic rat model for tauopathies and from age-matched control animals...
September 21, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28934392/nceh-1-modulates-cholesterol-metabolism-and-protects-against-%C3%AE-synuclein-toxicity-in-a-c-elegans-model-of-parkinson-s-disease
#10
Siyuan Zhang, Samantha A Glukhova, Kim A Caldwell, Guy A Caldwell
Parkinson's disease (PD) is an aging-associated neurodegenerative disease affecting millions worldwide. Misfolding, oligomerization and accumulation of the human α-synuclein protein is a key pathological hallmark of PD and is associated with the progressive loss of dopaminergic neurons over the course of aging. Lifespan extension via the suppression of IGF-1/insulin-like signaling (IIS) offers a possibility to retard disease onset through induction of metabolic changes that provide neuroprotection. The nceh-1 gene of Caenorhabditis elegans encodes an ortholog of neutral cholesterol ester hydrolase 1 (NCEH-1), an IIS downstream protein that was identified in a screen as a modulator of α-synuclein accumulation in vivo...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934388/loss-of-slc25a46-causes-neurodegeneration-by-affecting-mitochondrial-dynamics-and-energy-production-in-mice
#11
Zhuo Li, Yanyan Peng, Robert B Hufnagel, Yueh-Chiang Hu, Chuntao Zhao, Luis F Queme, Zaza Khuchua, Ashley M Driver, Fei Dong, Q Richard Lu, Diana M Lindquist, Michael P Jankowski, Rolf W Stottmann, Winston W Y Kao, Taosheng Huang
Recently, we identified biallelic mutations of SLC25A46 in patients with multiple neuropathies. Functional studies revealed that SLC25A46 may play an important role in mitochondrial dynamics by mediating mitochondrial fission. However, the cellular basis and pathogenic mechanism of the SLC25A46-related neuropathies are not fully understood. Thus, we generated a Slc25a46 knock-out mouse model. Mice lacking SLC25A46 displayed severe ataxia, mainly caused by degeneration of Purkinje cells. Increased numbers of small, unmyelinated and degenerated optic nerves as well as loss of retinal ganglion cells indicated optic atrophy...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28933786/pink1-interacts-with-%C3%AE-synuclein-and-abrogates-%C3%AE-synuclein-induced-neurotoxicity-by-activating-autophagy
#12
Jia Liu, Xue Wang, Yongquan Lu, Chunli Duan, Ge Gao, Lingling Lu, Hui Yang
Parkinson's disease (PD) is one of the most common neurodegenerative diseases, characterized by degeneration of dopaminergic neurons in the substantia nigra. α-synuclein (α-syn) and PTEN-induced putative kinase (PINK)1 are two critical proteins associated with the pathogenesis of PD. α-syn induces mitochondrial deficits and apoptosis, PINK1 was found to alleviate α-syn-induced toxicity, but the mechanistic details remain obscure. Here, we show that PINK1 interacts with α-syn mainly in the cytoplasm, where it initiates autophagy...
September 21, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28933411/mitochondrial-dysfunction-in-lysosomal-storage-disorders
#13
REVIEW
Mario de la Mata, David Cotán, Marina Villanueva-Paz, Isabel de Lavera, Mónica Álvarez-Córdoba, Raquel Luzón-Hidalgo, Juan M Suárez-Rivero, Gustavo Tiscornia, Manuel Oropesa-Ávila
Lysosomal storage diseases (LSDs) describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS), where neuronal dysfunction or loss results in progressive neurodegeneration and premature death...
October 11, 2016: Diseases (Basel)
https://www.readbyqxmd.com/read/28933365/milk-s-role-as-an-epigenetic-regulator-in-health-and-disease
#14
REVIEW
Bodo C Melnik, Gerd Schmitz
It is the intention of this review to characterize milk's role as an epigenetic regulator in health and disease. Based on translational research, we identify milk as a major epigenetic modulator of gene expression of the milk recipient. Milk is presented as an epigenetic "doping system" of mammalian development. Milk exosome-derived micro-ribonucleic acids (miRNAs) that target DNA methyltransferases are implicated to play the key role in the upregulation of developmental genes such as FTO, INS, and IGF1. In contrast to miRNA-deficient infant formula, breastfeeding via physiological miRNA transfer provides the appropriate signals for adequate epigenetic programming of the newborn infant...
March 15, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28933311/mg17-a-novel-triazole-derivative-abrogated-neuroinflammation-and-related-neurodegenerative-symptoms-in-rodents
#15
Gangadhar Matharasala, Ganesh Samala, Yogeeswari Perumal
The objective of present study is to explore multiple effects of the compound MG17 and relate them to achieve better therapeutic potential against neuroinflammation related disorders. We examined whether our compound is acting through regulating neuroinflammatory mediators. We have done some preliminary behavioral studies to shortlist the derivatives using rodent models of peripheral nerve injury in our earlier publication and now we extended our screening studies to explore the test compounds efficacy on other related peripheral neurological disorders such as Streptozotocin-induced diabetic peripheral neuropathy (DPN) and methyl mercury (MeHg) induced neurodegeneration in rats...
September 19, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28933272/evaluation-of-metabolic-and-synaptic-dysfunction-hypotheses-of-alzheimer-s-disease-ad-a-meta-analysis-of-csf-markers
#16
Roni Manyevitch, Matthew Protas, Sean Scarpiello, Marisa Deliso, Brittany Bass, Anthony Nanajian, Matthew Chang, Stefani M Thompson, Neil Khoury, Rachel Gonnella, Margit Trotz, D Blaine Moore, Emily Harms, George Perry, Lucy Clunes, Angélica Ortiz, Jan O Friedrich, Ian V J Murray
BACKGROUND: Alzheimer's disease (AD) is currently incurable and a majority of investigational drugs have failed clinical trials. One explanation for this failure may be the invalidity of hypotheses focusing on amyloid to explain AD pathogenesis. Recently, hypotheses which are centered on synaptic and metabolic dysfunction are increasingly implicated in AD. OBJECTIVE: Evaluate AD hypotheses by comparing neurotransmitter and metabolite marker concentrations in normal versus AD CSF...
September 21, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28933223/genetic-and-histological-alterations-reveal-key-role-of-prostaglandin-synthase-and-cyclooxygenase-1-and-2-in-traumatic-brain-injury-induced-neuroinflammation-in-the-cerebral-cortex-of-rats-exposed-to-moderate-fluid-percussion-injury
#17
Hideki Shojo, Cesario V Borlongan, Tadashi Mabuchi
After the initial insult in traumatic brain injury (TBI), secondary neurodegeneration occurs that is intimately associated with neuroinflammation. Prostaglandin (PG) synthases and cyclooxygenase (COX) 1 and 2 may contribute to inflammation in the brain. Temporal and spatial expression features of PG and COX1 and 2 following trauma may guide the development of antineuroinflammation strategies. Here, we examined PG synthase signaling and COX1 and 2 gene expression levels and COX-1- and 2-positive cell types and their temporal localization in TBI-induced brain in an effort to reveal their participation in the disease's evolving neuroinflammation...
July 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28933217/implantation-of-brain-derived-extracellular-matrix-enhances-neurological-recovery-after-traumatic-brain-injury
#18
Yun Wu, Jiayin Wang, Yejie Shi, Hongjian Pu, Rehana K Leak, Anthony K F Liou, Stephen F Badylak, Zhixiong Liu, Jun Zhang, Jun Chen, Ling Chen
Scaffolds composed of extracellular matrix (ECM) are being investigated for their ability to facilitate brain tissue remodeling and repair following injury. The present study tested the hypothesis that the implantation of brain-derived ECM would attenuate experimental traumatic brain injury (TBI) and explored potential underlying mechanisms. TBI was induced in mice by a controlled cortical impact (CCI). ECM was isolated from normal porcine brain tissue by decellularization methods, prepared as a hydrogel, and injected into the ipsilesional corpus callosum and striatum 1 h after CCI...
July 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28933033/sleep-disturbance-after-tbi
#19
REVIEW
Surendra Barshikar, Kathleen R Bell
PURPOSE OF REVIEW: Present relevant literature to update knowledge on sleep science, identify common sleep disturbances seen in TBI, discuss evidence for available treatment options, and illuminate future areas for research. RECENT FINDINGS: Sleep disturbances, including insomnia, circadian rhythm disturbances, and sleep apnea, are prevalent for all severities of traumatic brain injury (TBI), can be chronic, and affect both rehabilitation and recovery from the TBI...
September 20, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28932395/japanese-wdr45-de-novo-mutation-diagnosed-by-exome-analysis-a-case-report
#20
Hironobu Endo, Takeshi Uenaka, Wataru Satake, Yutaka Suzuki, Hisatsugu Tachibana, Norio Chihara, Takehiro Ueda, Kenji Sekiguchi, Taniguchi-Ikeda Mariko, Hisatomo Kowa, Fumio Kanda, Tatsushi Toda
A 40-year-old Japanese woman presented with slowly progressing parkinsonism in adulthood. She had a history of epilepsy with intellectual disability in childhood. In a head magnetic resonance scan, T2-weighted imaging showed low signal intensity areas in the globus pallidus and the substantia nigra; T1-weighted imaging showed a halo in the nigra. Because the patient's symptoms and history were similar to those of patients with neurodegeneration with brain iron accumulation, we ran an exome analysis to investigate neurodegeneration with brain iron accumulation-associated genes...
July 2017: Neurology and Clinical Neuroscience
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