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https://www.readbyqxmd.com/read/29678547/pamam-dendrimers-as-a-carbamazepine-delivery-system-for-neurodegenerative-diseases-a-biophysical-and-nanotoxicological-characterization
#1
Daniela E Igartúa, Carolina S Martinez, C Facundo Temprana, Silvia Del V Alonso, M Jimena Prieto
Carbamazepine (CBZ) is an antiepileptic drug, which also could be used in the treatment of neurodegenerative diseases, such as the Alzheimer's disease. However, its use has been limited due to its low solubility, inefficient pharmacokinetic profiles, and multiple side effects. PAMAM dendrimers, ethylenediamine core, generation 4.0 (amine terminal groups) and 4.5 (carboxylate terminal groups) (DG4.0 and DG4.5 respectively) are polymers that can increase drug solubility through complexation. Thus, the aim of this work was to obtain and characterize complexes between CBZ and dendrimers...
April 17, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29587262/whole-genome-linkage-analysis-with-whole-exome-sequencing-identifies-a-novel-frameshift-variant-in-nefh-in-a-chinese-family-with-charcot-marie-tooth-2-a-novel-variant-in-nefh-for-charcot-marie-tooth-2
#2
Xianli Bian, Pengfei Lin, Jiangxia Li, Feng Long, Ruonan Duan, Qianqian Yuan, Yan Li, Fei Gao, Shang Gao, Shijun Wei, Xi Li, Wenjie Sun, Yaoqin Gong, Chuanzhu Yan, Qiji Liu
BACKGROUND: Charcot-Marie-Tooth disease (CMT) is the most common neurodegenerative disorder of the peripheral nervous system. More than 50 genes/loci were found associated with the disease. We found a family with autosomal-dominant CMT2. OBJECTIVE: To reveal the pathogenic gene of the family and further investigate the function of the variant. METHODS: DNA underwent whole-genome linkage analysis for all family members and whole-exome sequencing for 2 affected members...
March 27, 2018: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/29568517/surfen-and-oxalyl-surfen-decrease-tau-hyperphosphorylation-and-mitigate-neuron-deficits-in-vivo-in-a-zebrafish-model-of-tauopathy
#3
Seyedeh Maryam Alavi Naini, Constantin Yanicostas, Rahma Hassan-Abdi, Sébastien Blondeel, Mohamed Bennis, Ryan J Weiss, Yitzhak Tor, Jeffrey D Esko, Nadia Soussi-Yanicostas
Background: Tauopathies comprise a family of neurodegenerative disorders including Alzheimer's disease for which there is an urgent and unmet need for disease-modifying treatments. Tauopathies are characterized by pathological tau hyperphosphorylation, which has been shown to correlate tightly with disease progression and memory loss in patients suffering from Alzheimer's disease. We recently demonstrated an essential requirement for 3- O -sulfated heparan sulfate in pathological tau hyperphosphorylation in zebrafish, a prominent model organism for human drug discovery...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29525604/astroglial-dj-1-over-expression-up-regulates-proteins-involved-in-redox-regulation-and-is-neuroprotective-in-vivo
#4
Ann Kristin Frøyset, Amanda J Edson, Naouel Gharbi, Essa A Khan, Daniel Dondorp, Qing Bai, Ettore Tiraboschi, Maximiliano L Suster, Joanne B Connolly, Edward A Burton, Kari E Fladmark
DJ-1, a Parkinson's disease-associated protein, is strongly up-regulated in reactive astrocytes in Parkinson's disease. This is proposed to represent a neuronal protective response, although the mechanism has not yet been identified. We have generated a transgenic zebrafish line with increased astroglial DJ-1 expression driven by regulatory elements from the zebrafish GFAP gene. Larvae from this transgenic line are protected from oxidative stress-induced injuries as caused by MPP+ , a mitochondrial complex I inhibitor shown to induce dopaminergic cells death...
February 17, 2018: Redox Biology
https://www.readbyqxmd.com/read/29522770/therapeutic-evaluation-of-solid-lipid-nanoparticle-of-quercetin-in-pentylenetetrazole-induced-cognitive-impairment-of-zebrafish
#5
Narahari Rishitha, Arunachalam Muthuraman
BACKGROUND: Quercetin is a major flavonoid in various plants. It possesses the multiple pharmacological actions like vascular integrity and regulatory action of the blood-brain barrier. AIMS: The present study is focused on evaluating the role of solid lipid nanoparticle of quercetin in pentylenetetrazole (PTZ) induced cognitive impairment of Danio rerio species. MAIN METHODS: The memory impairment of zebrafish was induced by exposing of PTZ in 7...
March 6, 2018: Life Sciences
https://www.readbyqxmd.com/read/29490693/a-hypomorphic-inherited-pathogenic-variant-in-ddx3x-causes-male-intellectual-disability-with-additional-neurodevelopmental-and-neurodegenerative-features
#6
Georgios Kellaris, Kamal Khan, Shahid M Baig, I-Chun Tsai, Francisca Millan Zamora, Paul Ruggieri, Marvin R Natowicz, Nicholas Katsanis
BACKGROUND: Intellectual disability (ID) is a common condition with a population prevalence frequency of 1-3% and an enrichment for males, driven in part by the contribution of mutant alleles on the X-chromosome. Among the more than 500 genes associated with ID, DDX3X represents an outlier in sex specificity. Nearly all reported pathogenic variants of DDX3X are de novo, affect mostly females, and appear to be loss of function variants, consistent with the hypothesis that haploinsufficiency at this locus on the X-chromosome is likely to be lethal in males...
March 1, 2018: Human Genomics
https://www.readbyqxmd.com/read/29464011/a-microfluidic-device-to-study-electrotaxis-and-dopaminergic-system-of-zebrafish-larvae
#7
Amir Reza Peimani, Georg Zoidl, Pouya Rezai
The zebrafish is a lower vertebrate model organism offering multiple applications for both fundamental and biomedical research into the nervous system from genes to behaviour. Investigation of zebrafish larvae's movement in response to various stimuli, which involves the dopaminergic system, is of interest in the field of sensory-motor integration. Nevertheless, the conventional methods of movement screening in Petri dishes and multi-well plates are mostly qualitative, uncontrollable, and inaccurate in terms of stimulus delivery and response analysis...
January 2018: Biomicrofluidics
https://www.readbyqxmd.com/read/29449560/knockout-of-zebrafish-interleukin-7-receptor-il7r-by-the-crispr-cas9-system-delays-retinal-neurodevelopment
#8
Shijiao Cai, Yang Chen, Yue Shang, Jianlin Cui, Zongjin Li, Yuhao Li
Interleukin 7 receptor (il7r), a transmembrane receptor, belongs to the type I cytokine receptor family. Il7r is involved in the pathogenesis of neurodegenerative disorders, such as multiple sclerosis. Targeted knockdown of il7r leads to delayed myelination, highlighting the potential role of il7r in the development of the nervous system. Zebrafish is an ideal model for the study of neurogenesis; moreover, the il7r gene is highly conserved between zebrafish and human. The aim of the present study was to investigate the novel function of il7r in neurogenesis...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29419415/spliceosomal-components-protect-embryonic-neurons-from-r-loop-mediated-dna-damage-and-apoptosis
#9
Shelly Sorrells, Sara Nik, Mattie Casey, Rosannah C Cameron, Harold Truong, Cristhian Toruno, Michelle Gulfo, Albert Lowe, Cicely Jette, Rodney A Stewart, Teresa V Bowman
RNA splicing factors are essential for the viability of all eukaryotic cells; however, in metazoans some cell types are exquisitely sensitive to disruption of splicing factors. Neuronal cells represent one such cell type, and defects in RNA splicing factors can lead to neurodegenerative diseases. The basis for this tissue selectivity is not well understood owing to difficulties in analyzing the consequences of splicing factor defects in whole-animal systems. Here, we use zebrafish mutants to show that loss of spliceosomal components, including splicing factor 3b, subunit 1 ( sf3b1 ), causes increased DNA double-strand breaks and apoptosis in embryonic neurons...
February 26, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29317240/toxicity-and-cardiac-effects-of-acute-exposure-to-tryptophan-metabolites-on-the-kynurenine-pathway-in-early-developing-zebrafish-danio-rerio-embryos
#10
Michal Majewski, Natalia Kasica, Anna Jakimiuk, Piotr Podlasz
Defects in tryptophan metabolism on the l-kynurenine pathway (KP) are implicated in a number of human diseases, including chronic kidney disease, brain edema or injury, tuberculosis and malaria - as well as cancer, neurodegenerative and autoimmune disorders. However, it is unclear to what extent detrimental effects of exposure to tryptophan metabolites might impact the early development of organism. Thus, this study examined the effects of KP exposure in zebrafish embryos starting at the blastula period (4hpf) and the segmentation stage (24hpf)...
February 15, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29313599/neurodegeneration-in-zebrafish-embryos-and-adults-after-cadmium-exposure
#11
Antonio Monaco, Teresa Capriello, Maria C Grimaldi, Valentina Schiano, Ida Ferrandino
Cadmium is a biologically non-essential metal. It is also toxic to many organs including the brain. The aim of this study was to analyse the neurodegenerative effects of this metal in embryos and adults of zebrafish exposed to sub-lethal concentrations of cadmium. The study was performed by cytochemical stainings. Six hours after fertilisation (hpf) zebrafish embryos were treated for 24 hours with 9 μM of cadmium and subsequently stained with Acridine orange in whole mount to detect apoptosis in the brain...
October 19, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/29285938/novel-kunitz-like-peptides-discovered-in-the-zoanthid-palythoa-caribaeorum-through-transcriptome-sequencing
#12
Qiwen Liao, Shengnan Li, Shirley Weng In Siu, Binrui Yang, Chen Huang, Judy Yuet-Wa Chan, Jean-Étienne R L Morlighem, Clarence Tsun Ting Wong, Gandhi Rádis-Baptista, Simon Ming-Yuen Lee
Palythoa caribaeorum (class Anthozoa) is a zoanthid that together jellyfishes, hydra, and sea anemones, which are venomous and predatory, belongs to the Phyllum Cnidaria. The distinguished feature in these marine animals is the cnidocytes in the body tissues, responsible for toxin production and injection that are used majorly for prey capture and defense. With exception for other anthozoans, the toxin cocktails of zoanthids have been scarcely studied and are poorly known. Here, on the basis of the analysis of P...
February 2, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29239312/endogenous-retinal-neural-stem-cell-reprogramming-for-neuronal-regeneration
#13
REVIEW
Romain Madelaine, Philippe Mourrain
In humans, optic nerve injuries and associated neurodegenerative diseases are often followed by permanent vision loss. Consequently, an important challenge is to develop safe and effective methods to replace retinal neurons and thereby restore neuronal functions and vision. Identifying cellular and molecular mechanisms allowing to replace damaged neurons is a major goal for basic and translational research in regenerative medicine. Contrary to mammals, the zebrafish has the capacity to fully regenerate entire parts of the nervous system, including retina...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29230019/metabolic-profiling-of-zebrafish-danio-rerio-embryos-by-nmr-spectroscopy-reveals-multifaceted-toxicity-of-%C3%AE-methylamino-l-alanine-bmaa
#14
Upasana Roy, Laura Conklin, Jürgen Schiller, Jörg Matysik, John P Berry, A Alia
β-methylamino-L-alanine (BMAA) has been linked to several interrelated neurodegenerative diseases. Despite considerable research, specific contributions of BMAA toxicity to neurodegenerative diseases remain to be fully resolved. In the present study, we utilized state-of-the-art high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR), applied to intact zebrafish (Danio rerio) embryos, as a model of vertebrate development, to elucidate changes in metabolic profiles associated with BMAA exposure...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29199130/the-neurological-toxicity-of-heavy-metals-a-fish-perspective
#15
Adrian J Green, Antonio Planchart
The causes of neurodegenerative diseases are complex with likely contributions from genetic susceptibility and environmental exposures over an organism's lifetime. In this review, we examine the role that aquatic models, especially zebrafish, have played in the elucidation of mechanisms of heavy metal toxicity and nervous system function over the last decade. Focus is applied to cadmium, lead, and mercury as significant contributors to central nervous system morbidity, and the application of numerous transgenic zebrafish expressing fluorescent reporters in specific neuronal populations or brain regions enabling high-resolution neurodevelopmental and neurotoxicology research...
December 1, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29157806/trigonelline-promotes-auditory-function-through-nerve-growth-factor-signaling-on-diabetic-animal-models
#16
Rodrigo Castañeda, Isabel Rodriguez, Youn Hee Nam, Bin Na Hong, Tong Ho Kang
BACKGROUND: Protection of cochlear function and reconstruction of neuronal networks in damaged auditory sensory structures is crucial for therapeutic treatment of diabetic hearing loss. Nerve growth factor (NGF) has been used as a novel therapeutic target to protect against the neurodegenerative effects of Diabetes Mellitus (DM). PURPOSE: We aimed to evaluate the potential effect of trigonelline (TRG) on reducing auditory damage produced by DM using NGF as a potential marker...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29155703/modeling-amyloid-%C3%AE-42-toxicity-and-neurodegeneration-in-adult-zebrafish-brain
#17
Prabesh Bhattarai, Alvin Kuriakose Thomas, Mehmet Ilyas Cosacak, Christos Papadimitriou, Violeta Mashkaryan, Yixin Zhang, Caghan Kizil
Alzheimer's disease (AD) is a debilitating neurodegenerative disease in which accumulation of toxic amyloid-β42 (Aβ42) peptides leads to synaptic degeneration, inflammation, neuronal death, and learning deficits. Humans cannot regenerate lost neurons in the case of AD in part due to impaired proliferative capacity of the neural stem/progenitor cells (NSPCs) and reduced neurogenesis. Therefore, efficient regenerative therapies should also enhance the proliferation and neurogenic capacity of NSPCs. Zebrafish (Danio rerio) is a regenerative organism, and we can learn the basic molecular programs with which we could design therapeutic approaches to tackle AD...
October 25, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29151170/the-function-of-the-cellular-prion-protein-in-health-and-disease
#18
REVIEW
Joel C Watts, Matthew E C Bourkas, Hamza Arshad
The essential role of the cellular prion protein (PrPC ) in prion disorders such as Creutzfeldt-Jakob disease is well documented. Moreover, evidence is accumulating that PrPC may act as a receptor for protein aggregates and transduce neurotoxic signals in more common neurodegenerative disorders, such as Alzheimer's disease. Although the pathological roles of PrPC have been thoroughly characterized, a general consensus on its physiological function within the brain has not yet been established. Knockout studies in various organisms, ranging from zebrafish to mice, have implicated PrPC in a diverse range of nervous system-related activities that include a key role in the maintenance of peripheral nerve myelination as well as a general ability to protect against neurotoxic stimuli...
February 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29079063/neuroprotective-and-neuro-restorative-effects-of-minocycline-and-rasagiline-in-a-zebrafish-6-hydroxydopamine-model-of-parkinson-s-disease
#19
Aileen Cronin, Maura Grealy
Parkinson's disease is a common, debilitating, neurodegenerative disorder for which the current gold standard treatment, levodopa (L-DOPA) is symptomatic. There is an urgent, unmet need for neuroprotective or, ideally, neuro-restorative drugs. We describe a 6-hydroxydopamine (6-OHDA) zebrafish model to screen drugs for neuroprotective and neuro-restorative capacity. Zebrafish larvae at two days post fertilization were exposed to 6-OHDA for three days, with co-administration of test drugs for neuroprotection experiments, or for 32 h, with subsequent treatment with test drugs for neuro-restoration experiments...
December 26, 2017: Neuroscience
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
#20
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
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