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https://www.readbyqxmd.com/read/29353068/mitochondrial-atp-sensitive-potassium-channel-regulates-mitochondrial-dynamics-to-participate-in-neurodegeneration-of-parkinson-s-disease
#1
Kaige Peng, Jun Hu, Jingsong Xiao, Guorong Dan, Likui Yang, Feng Ye, Zhongmin Zou, Jia Cao, Yan Sai
Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. Mitochondrial dysfunction has been the focus of the pathogenesis of PD. The mitochondrial ATP-sensitive potassium channel (mitoKATP) plays a significant role in mitochondrial physiology and has been extensively shown to protect against ischemic and brain reperfusion injury. However, there have long been controversies regarding its role in Parkinson's disease. We investigated the role of mitoKATP channels in rotenone-induced PD model in vivo and vitro and the interactions of mitoKATP channels, mitochondrial dynamics and PD...
January 15, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29352267/differential-susceptibility-of-striatal-hippocampal-and-cortical-neurons-to-caspase-6
#2
Anastasia Noël, Libin Zhou, Bénédicte Foveau, P Jesper Sjöström, Andréa C LeBlanc
Active cysteinyl protease Caspase-6 is associated with early Alzheimer and Huntington diseases. Higher entorhinal cortex and hippocampal Caspase-6 levels correlate with lower cognitive performance in aged humans. Caspase-6 induces axonal degeneration in human primary neuron cultures and causes inflammation and neurodegeneration in mouse hippocampus, and age-dependent memory impairment. To assess whether Caspase-6 causes damage to another neuronal system, a transgenic knock-in mouse overexpressing a self-activated form of Caspase-6 five-fold in the striatum, the area affected in Huntington disease, and 2...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352205/2-5-hexanedione-induces-dopaminergic-neurodegeneration-through-integrin-%C3%AE-m%C3%AE-2-nadph-oxidase-axis-mediated-microglial-activation
#3
Cong Zhang, Liyan Hou, Jie Yang, Yuning Che, Fuqiang Sun, Huihua Li, Qingshan Wang
Recent study demonstrated that chronic exposure to solvents increases the risk of Parkinson's disease (PD), the second most common neurodegenerative disorder characterized by progressive dopaminergic neurodegeneration in the substantia nigra (SN). n-Hexane, a widely used organic solvent, displays central-peripheral neurotoxicity, which is mainly mediated by its active metabolite, 2,5-hexanedione (HD). However, whether HD exposure contributes to PD remains unclear. In this study, we found that rats exposed to HD displayed progressive dopaminergic neurodegeneration in the nigrostriatal system...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29351877/rest-a-master-transcriptional-regulator-in-neurodegenerative-disease
#4
REVIEW
Jee-Yeon Hwang, R Suzanne Zukin
The restrictive element-1 silencing transcription factor)/NRSF (neuron-restrictive silencing factor (NRSF) is a transcriptional repressor which acts via epigenetic remodeling to silence target genes. Emerging evidence indicates that REST is a master transcriptional regulator of neuron-specific genes not only in neurogenesis and neuronal differentiation, but also in differentiated neurons during the critical period in postnatal brain development, where it plays a role in fine-tuning of genes involved in synaptic plasticity, and in normal aging, where it promotes neuroprotection by repressing genes involved in oxidative stress and β-amyloid toxicity...
January 16, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29351706/micrornas-and-target-genes-in-pituitary-adenomas
#5
Yajuan Feng, Zhi-Gang Mao, Xin Wang, Qiu Du, Mengyao Jian, Dimin Zhu, Zheng Xiao, Hai-Jun Wang, Yong-Hong Zhu
Pituitary adenomas account for the top three primary intracranial tumors in terms of total incidence rates. The clinical symptoms presented by the disease are often characterized by a series of systemic endocrine disorders, severe occupational lesions, and even some malignant features, and therefore early diagnosis and predicting recurrence would be instructive for clinical treatment of pituitary adenomas. An increasing number of specific microRNA (miRNA) expression signatures have been identified in pituitary, and miRNAs are related with the pituitary tumorigenesis, dysfunction, neurodegeneration, and metastatic non-functioning pituitary carcinoma...
January 19, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29350438/astrocytic-glutamine-synthetase-is-expressed-in-the-neuronal-somatic-layers-and-down-regulated-proportionally-to-neuronal-loss-in-the-human-epileptic-hippocampus
#6
Ismini E Papageorgiou, Nektarios A Valous, Bernd Lahrmann, Hana Janova, Zin-Juan Klaft, Arend Koch, Ulf C Schneider, Peter Vajkoczy, Frank L Heppner, Niels Grabe, Niels Halama, Uwe Heinemann, Oliver Kann
Human mesial temporal lobe epilepsy (MTLE) features subregion-specific hippocampal neurodegeneration and reactive astrogliosis, including up-regulation of the glial fibrillary acidic protein (GFAP) and down-regulation of glutamine synthetase (GS). However, the regional astrocytic expression pattern of GFAP and GS upon MTLE-associated neurodegeneration still remains elusive. We assessed GFAP and GS expression in strict correlation with the local neuronal number in cortical and hippocampal surgical specimens from 16 MTLE patients using immunohistochemistry, stereology and high-resolution image analysis for digital pathology and whole-slide imaging...
January 19, 2018: Glia
https://www.readbyqxmd.com/read/29349574/pacific-ciguatoxin-induces-excitotoxicity-and-neurodegeneration-in-the-motor-cortex-via-caspase-3-activation-implication-for-irreversible-motor-deficit
#7
Pallavi Asthana, Ni Zhang, Gajendra Kumar, Virendra Bhagawan Chine, Kunal Kumar Singh, Yim Ling Mak, Leo Lai Chan, Paul Kwan Sing Lam, Chi Him Eddie Ma
Consumption of fish containing ciguatera toxins or ciguatoxins (CTXs) causes ciguatera fish poisoning (CFP). In some patients, CFP recurrence occurs even years after exposure related to CTXs accumulation. Pacific CTX-1 (P-CTX-1) is one of the most potent natural substances known that causes predominantly neurological symptoms in patients; however, the underlying pathogenies of CFP remain unknown. Using clinically relevant neurobehavioral tests and electromyography (EMG) to assess effects of P-CTX-1 during the 4 months after exposure, recurrent motor strength deficit occurred in mice exposed to P-CTX-1...
January 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29348375/-suspected-non-alzheimer-s-disease-pathophysiology-snap-and-its-pathological-backgrounds-in-the-diagnosis-of-preclinical-and-clinical-alzheimer-s-disease
#8
Masahito Yamada
Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker-based condition that is found in individuals with normal levels of amyloid-β protein (Aβ) markers (A-) and abnormal levels of markers of neurodegeneration or neuronal injury (N+). SNAP is found in 20-26% of cognitively normal (CN) individuals aged 65 years or older and 17-35% of individuals with mild cognitive impairment (MCI). Similarly, 7-39% of patients with clinically probable Alzheimer's disease (AD) dementia are negative for Aβ...
January 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29348018/myocardial-inflammation-predicts-remodeling-and-neuroinflammation-after-myocardial-infarction
#9
James T Thackeray, Henri C Hupe, Yong Wang, Jens P Bankstahl, Georg Berding, Tobias L Ross, Johann Bauersachs, Kai C Wollert, Frank M Bengel
BACKGROUND: The local inflammatory tissue response after acute myocardial infarction (MI) determines subsequent healing. Systemic interaction may induce neuroinflammation as a precursor to neurodegeneration. OBJECTIVES: This study sought to assess the influence of MI on cardiac and brain inflammation using noninvasive positron emission tomography (PET) of the heart-brain axis. METHODS: After coronary artery ligation or sham surgery, mice (n = 49) underwent serial whole-body PET imaging of the mitochondrial translocator protein (TSPO) as a marker of activated macrophages and microglia...
January 23, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29346778/diverse-brain-myeloid-expression-profiles-reveal-distinct-microglial-activation-states-and-aspects-of-alzheimer-s-disease-not-evident-in-mouse-models
#10
Brad A Friedman, Karpagam Srinivasan, Gai Ayalon, William J Meilandt, Han Lin, Melanie A Huntley, Yi Cao, Seung-Hye Lee, Patrick C G Haddick, Hai Ngu, Zora Modrusan, Jessica L Larson, Joshua S Kaminker, Marcel P van der Brug, David V Hansen
Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer's disease (AD) model, we identified microglial subsets-distinct from previously reported "disease-associated microglia"-expressing interferon-related or proliferation modules...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346382/6-ohda-induced-dopaminergic-neurodegeneration-in-caenorhabditis-elegans-is-promoted-by-the-engulfment-pathway-and-inhibited-by-the-transthyretin-related-protein-ttr-33
#11
Sarah-Lena Offenburger, Xue Yan Ho, Theresa Tachie-Menson, Sean Coakley, Massimo A Hilliard, Anton Gartner
Oxidative stress is linked to many pathological conditions including the loss of dopaminergic neurons in Parkinson's disease. The vast majority of disease cases appear to be caused by a combination of genetic mutations and environmental factors. We screened for genes protecting Caenorhabditis elegans dopaminergic neurons from oxidative stress induced by the neurotoxin 6-hydroxydopamine (6-OHDA) and identified the transthyretin-related gene ttr-33. The only described C. elegans transthyretin-related protein to date, TTR-52, has been shown to mediate corpse engulfment as well as axon repair...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29346364/mutations-in-caenorhabditis-elegans-neuroligin-like-glit-1-the-apoptosis-pathway-and-the-calcium-chaperone-crt-1-increase-dopaminergic-neurodegeneration-after-6-ohda-treatment
#12
Sarah-Lena Offenburger, Elisabeth Jongsma, Anton Gartner
The loss of dopaminergic neurons is a hallmark of Parkinson's disease, the aetiology of which is associated with increased levels of oxidative stress. We used C. elegans to screen for genes that protect dopaminergic neurons against oxidative stress and isolated glit-1 (gliotactin (Drosophila neuroligin-like) homologue). Loss of the C. elegans neuroligin-like glit-1 causes increased dopaminergic neurodegeneration after treatment with 6-hydroxydopamine (6-OHDA), an oxidative-stress inducing drug that is specifically taken up into dopaminergic neurons...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29346273/report-on-the-symposium-molecular-mechanisms-involved-in-neurodegeneration
#13
Giselle Pentón-Rol, Majel Cervantes-Llanos
The prevalence of neurodegenerative diseases is currently a major concern in public health because of the lack of neuroprotective and neuroregenerative drugs. The symposium on Molecular Mechanisms Involved in Neurodegeneration held in Varadero, Cuba, updated the participants on the basic mechanisms of neurodegeneration, on the different approaches for drug discovery, and on early research results on therapeutic approaches for the treatment of neurodegenerative diseases. Alzheimer's disease and in silico research were covered by many of the presentations in the symposium, under the umbrella of the "State of the Art of Non-clinical Models for Neurodegenerative Diseases" International Congress, held from 20 to 24 June 2017...
January 18, 2018: Behavioral Sciences
https://www.readbyqxmd.com/read/29345616/inhibition-of-oxidative-stress-in-cholinergic-projection-neurons-fully-rescues-aging-associated-olfactory-circuit-degeneration-in-drosophila
#14
Ashiq Hussain, Atefeh Pooryasin, Mo Zhang, Laura F Loschek, Marco La Fortezza, Anja B Friedrich, Catherine-Marie Blais, Habibe K Üçpunar, Vicente A Yépez, Martin Lehmann, Nicolas Gompel, Julien Gagneur, Stephan J Sigrist, Ilona C Grunwald Kadow
Loss of the sense of smell is among the first signs of natural aging and neurodegenerative diseases such as Alzheimer's and Parkinson's. Cellular and molecular mechanisms promoting this smell loss are not understood. Here, we show that Drosophila melanogaster also loses olfaction before vision with age. Within the olfactory circuit, cholinergic projection neurons show a reduced odor response accompanied by a defect in axonal integrity and reduction in synaptic marker proteins. Using behavioral functional screening, we pinpoint that expression of the mitochondrial reactive oxygen scavenger SOD2 in cholinergic projection neurons is necessary and sufficient to prevent smell degeneration in aging flies...
January 18, 2018: ELife
https://www.readbyqxmd.com/read/29345217/statistical-analysis-of-human-microarray-data-shows-that-dietary-intervention-with-n-3-fatty-acids-flavonoids-and-resveratrol-enriches-for-immune-response-and-disease-pathways
#15
Alix Warburton, Olga Vasieva, Peter Quinn, James P Stewart, John P Quinn
n-3 Fatty acids, flavonoids and resveratrol are well publicised for their beneficial effects on human health and wellbeing. Identifying common, underlying biological mechanisms targeted by these functional foods would therefore be informative for the public health sector for advising on nutritional health and disease, food and drug product development and consumer interest. The aim of this study was to explore the potential effects of gene expression changes associated with n-3 fatty acids EPA and DHA, flavonoids and resveratrol on modifying biological systems and disease pathways...
January 18, 2018: British Journal of Nutrition
https://www.readbyqxmd.com/read/29344929/pla2g6-deficiency-in-zebrafish-leads-to-dopaminergic-cell-death-axonal-degeneration-increased-%C3%AE-synuclein-expression-and-defects-in-brain-functions-and-pathways
#16
Elena Sánchez, Luis J Azcona, Coro Paisán-Ruiz
This study aimed to gain insights into the pathophysiology underlying PLA2G6-associated neurodegeneration that is implicated in three different neurological disorders, suggesting that other, unknown genetic or environmental factors might contribute to its wide phenotypic expression. To accomplish this, we downregulated the function of pla2g6 in the zebrafish nervous system, performed parkinsonism-related phenotypic characterization, and determined the effects of gene regulation upon the loss of pla2g6 function by using RNA sequencing and downstream analyses...
January 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29344865/isolation-of-distinct-types-of-neurons-from-fresh-brain-tissue-using-laser-microdissection-in-combination-with-high-performance-liquid-chromatography-mass-spectrometry
#17
Luisa Aring, Simone Steinbach, Katrin Marcus, Caroline May
Humans age and the ageing process affects cells in all areas of the human body, including nerve cells within the brain. With advancing age there is also a rise in the probability of developing a neurodegenerative disorder such as, e.g., amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, or Alzheimer's disease. In all these age-related neurodegenerative disorders, distinct neuron populations within specific brain regions are primarily affected. For example, Parkinson's disease is characterized by a slowly progressive degeneration of dopaminergic neurons in the substantia nigra whereas the entorhinal cortex is first affected in Alzheimer's disease...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29342882/implication-of-soluble-forms-of-cell-adhesion-molecules-in-infectious-disease-and-tumor-insights-from-transgenic-animal-models
#18
REVIEW
Etsuro Ono, Toshimitsu Uede
Cell adhesion molecules (CAMs) are surface ligands, usually glycoproteins, which mediate cell-to-cell adhesion. They play a critical role in maintaining tissue integrity and mediating migration of cells, and some of them also act as viral receptors. It has been known that soluble forms of the viral receptors bind to the surface glycoproteins of the viruses and neutralize them, resulting in inhibition of the viral entry into cells. Nectin-1 is one of important CAMs belonging to immunoglobulin superfamily and herpesvirus entry mediator (HVEM) is a member of the tumor necrosis factor (TNF) receptor family...
January 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29341299/autonomous-purkinje-cell-axonal-dystrophy-causes-ataxia-in-peroxisomal-multifunctional-protein-2-deficiency
#19
Stephanie De Munter, Dorien Bamps, Ana Rita Malheiro, Ritesh Kumar Baboota, Pedro Brites, Myriam Baes
BACKGROUND: Peroxisomes play a crucial role in normal neurodevelopment and in the maintenance of the adult brain. This depends largely on intact peroxisomal β-oxidation given the similarities in pathologies between peroxisome biogenesis disorders and deficiency of multifunctional protein-2 (MFP2), the central enzyme of this pathway. Recently, adult patients diagnosed with cerebellar ataxia were shown to have mild mutations in the MFP2 gene, hydroxy-steroid dehydrogenase (17 beta) type 4 (HSD17B4)...
January 17, 2018: Brain Pathology
https://www.readbyqxmd.com/read/29341269/characterization-of-a-3xtg-ad-mouse-model-of-alzheimer-s-disease-with-the-senescence-accelerated-mouse-prone-8-samp8-background
#20
Jessica Virgili, Meryem Lebbadi, Cyntia Tremblay, Isabelle St-Amour, Caroline Pierrisnard, Audrey Faucher-Genest, Vincent Emond, Carl Julien, Frédéric Calon
No model fully recapitulates the neuropathology of Alzheimer's disease (AD). Although the triple-transgenic mouse model of AD (3xTg-AD) expresses Aβ plaques and tau-laden neurofibrillary tangles, as well as synaptic and behavioral deficits, it does not display frank neuronal loss. Since old age is the most important risk factor in AD, senescence-related interactions might be lacking to truly establish an AD-like environment. To investigate this hypothesis, we bred the 3xTg-AD mouse with the senescence-accelerated mouse prone 8 (SAMP8), a model of accelerated aging...
January 17, 2018: Synapse
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