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Frontiers in Molecular Neuroscience

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https://www.readbyqxmd.com/read/28428745/decreased-levels-of-foldase-and-chaperone-proteins-are-associated-with-an-early-onset-amyotrophic-lateral-sclerosis
#1
Melania Filareti, Silvia Luotti, Laura Pasetto, Mauro Pignataro, Katia Paolella, Paolo Messina, Elisabetta Pupillo, Massimiliano Filosto, Christian Lunetta, Jessica Mandrioli, Giuseppe Fuda, Andrea Calvo, Adriano Chiò, Massimo Corbo, Caterina Bendotti, Ettore Beghi, Valentina Bonetto
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive upper and lower motor neuron degeneration. One of the peculiar clinical characteristics of ALS is the wide distribution in age of onset, which is probably caused by different combinations of intrinsic and exogenous factors. We investigated whether these modifying factors are converging into common pathogenic pathways leading either to an early or a late disease onset. This would imply the identification of phenotypic biomarkers, that can distinguish the two populations of ALS patients, and of relevant pathways to consider in a therapeutic intervention...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28428744/mutational-analysis-at-intersubunit-interfaces-of-an-anionic-glutamate-receptor-reveals-a-key-interaction-important-for-channel-gating-by-ivermectin
#2
Nurit Degani-Katzav, Revital Gortler, Marina Weissman, Yoav Paas
The broad-spectrum anthelmintic drug ivermectin (IVM) activates and stabilizes an open-channel conformation of invertebrate chloride-selective glutamate receptors (GluClRs), thereby causing a continuous inflow of chloride ions and sustained membrane hyperpolarization. These effects suppress nervous impulses and vital physiological processes in parasitic nematodes. The GluClRs are pentamers. Homopentameric receptors assembled from the Caenorhabditis elegans (C. elegans) GluClα (GLC-1) subunit can inherently respond to IVM but not to glutamate (the neurotransmitter)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28424588/chaperones-as-suppressors-of-protein-misfolded-oligomer-toxicity
#3
REVIEW
Benedetta Mannini, Fabrizio Chiti
Chaperones have long been recognized to play well defined functions such as to: (i) assist protein folding and promote formation and maintenance of multisubunit complexes; (ii) mediate protein degradation; (iii) inhibit protein aggregation; and (iv) promote disassembly of undesired aberrant protein aggregates. In addition to these well-established functions, it is increasingly clear that chaperones can also interact with aberrant protein aggregates, such as pre-fibrillar oligomers and fibrils, and inhibit their toxicity commonly associated with neurodegenerative diseases without promoting their disassembly...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28424587/interactions-of-the-mechanosensitive-channels-with-extracellular-matrix-integrins-and-cytoskeletal-network-in-osmosensation
#4
REVIEW
Runsheng Jiao, Dan Cui, Stephani C Wang, Dongyang Li, Yu-Feng Wang
Life is maintained in a sea water-like internal environment. The homeostasis of this environment is dependent on osmosensory system translation of hydromineral information into osmotic regulatory machinery at system, tissue and cell levels. In the osmosensation, hydromineral information can be converted into cellular reactions through osmoreceptors, which changes thirst and drinking, secretion of antidiuretic vasopressin (VP), reabsorption of water and salt in the kidneys at systemic level as well as cellular metabolic activity and survival status at tissue level...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28424586/app-protein-family-signaling-at-the-synapse-insights-from-intracellular-app-binding-proteins
#5
REVIEW
Suzanne Guénette, Paul Strecker, Stefan Kins
Understanding the molecular mechanisms underlying amyloid precursor protein family (APP/APP-like proteins, APLP) function in the nervous system can be achieved by studying the APP/APLP interactome. In this review article, we focused on intracellular APP interacting proteins that bind the YENPTY internalization motif located in the last 15 amino acids of the C-terminal region. These proteins, which include X11/Munc-18-interacting proteins (Mints) and FE65/FE65Ls, represent APP cytosolic binding partners exhibiting different neuronal functions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28424585/efr3a-insufficiency-attenuates-the-degeneration-of-spiral-ganglion-neurons-after-hair-cell-loss
#6
Haixia Hu, Bin Ye, Le Zhang, Quan Wang, Zhiwei Liu, Suying Ji, Qiuju Liu, Jingrong Lv, Yan Ma, Ying Xu, Hao Wu, Fude Huang, Mingliang Xiang
Sensorineural hearing loss (SNHL) is caused by an irreversible impairment of cochlear hair cells and subsequent progressive degeneration of spiral ganglion neurons (SGNs). Eighty-five requiring 3 (Efr3) is a plasma membrane protein conserved from yeast to human, and knockout of Efr3a was reported to facilitate the survival of hippocampal newborn neurons in adult mice. Previously, we found Efr3a expression in the auditory neural pathway is upregulated soon after the destruction of hair cells. Here we conducted a time-course analysis of drug-caused damage to hearing ability, hair cells and SGNs in Efr3a knocking down mice (Efr3a(-/+), Efr3a KD) and their wild type littermates...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28424584/hif-1%C3%AE-overexpression-improves-transplanted-bone-mesenchymal-stem-cells-survival-in-rat-mcao-stroke-model
#7
Bingke Lv, Feng Li, Jianbang Han, Jie Fang, Limin Xu, Chengmei Sun, Tian Hua, Zhongfei Zhang, Zhiming Feng, Xiaodan Jiang
Bone mesenchymal stem cells (BMSCs) death after transplantation is a serious obstacle impacting on the outcome of cell therapy for cerebral infarction. This study was aimed to investigate whether modification of BMSCs with hypoxia-inducible factor 1α (Hif-1α) could enhance the survival of the implanted BMSCs. BMSCs were isolated from Wistar rats, and were infected with Hif-1α-GFP lentiviral vector or Hif-1α siRNA. The modified BMSCs were exposed to oxygen-glucose deprivation (OGD) condition, cellular viability and apoptosis were then assessed...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28420964/identification-of-the-spinal-expression-profile-of-non-coding-rnas-involved-in-neuropathic-pain-following-spared-nerve-injury-by-sequence-analysis
#8
Jun Zhou, Qingming Xiong, Hongtao Chen, Chengxiang Yang, Youling Fan
Neuropathic pain (NP) is caused by damage to the nervous system, resulting in aberrant pain, which is associated with gene expression changes in the sensory pathway. However, the molecular mechanisms are not fully understood. A non-coding Ribose Nucleic Acid (ncRNA) is an RNA molecule that is not translated into a protein. NcRNAs are involved in many cellular processes, and mutations or imbalances of the repertoire within the body can cause a variety of diseases. Although ncRNAs have recently been shown to play a role in NP pathogenesis, the specific effects of ncRNAs in NP remain largely unknown...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28420963/rna-seq-analysis-of-microglia-reveals-time-dependent-activation-of-specific-genetic-programs-following-spinal-cord-injury
#9
Harun N Noristani, Yannick N Gerber, Jean-Charles Sabourin, Marine Le Corre, Nicolas Lonjon, Nadine Mestre-Frances, Hélène E Hirbec, Florence E Perrin
Neurons have inherent competence to regrow following injury, although not spontaneously. Spinal cord injury (SCI) induces a pronounced neuroinflammation driven by resident microglia and infiltrating peripheral macrophages. Microglia are the first reactive glial population after SCI and participate in recruitment of monocyte-derived macrophages to the lesion site. Both positive and negative influence of microglia and macrophages on axonal regeneration had been reported after SCI, raising the issue whether their response depends on time post-lesion or different lesion severity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28420962/dysregulation-of-rna-binding-protein-aggregation-in-neurodegenerative-disorders
#10
REVIEW
Brandon Maziuk, Heather I Ballance, Benjamin Wolozin
The unique biology of RNA binding proteins is altering our view of the genesis of protein misfolding diseases. These proteins use aggregation of low complexity domains (LCDs) as a means to regulate the localization and utilization of RNA by forming RNA granules, such as stress granules, transport granules and P-bodies. The reliance on reversible aggregation as a mechanism for biological regulation renders this family of proteins highly vulnerable to promoting diseases of protein misfolding. Mutations in RNA binding proteins are associated with many neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28420961/the-role-of-astrocytes-in-neuroprotection-after-brain-stroke-potential-in-cell-therapy
#11
REVIEW
Andrea Becerra-Calixto, Gloria P Cardona-Gómez
Astrocytes are commonly involved in negative responses through their hyperreactivity and glial scar formation in excitotoxic and/or mechanical injuries. But, astrocytes are also specialized glial cells of the nervous system that perform multiple homeostatic functions for the survival and maintenance of the neurovascular unit. Astrocytes have neuroprotective, angiogenic, immunomodulatory, neurogenic, and antioxidant properties and modulate synaptic function. This makes them excellent candidates as a source of neuroprotection and neurorestoration in tissues affected by ischemia/reperfusion, when some of their deregulated genes can be controlled...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28408867/visualization-of-snare-mediated-hemifusion-between-giant-unilamellar-vesicles-arrested-by-myricetin
#12
Paul Heo, Joon-Bum Park, Yeon-Kyun Shin, Dae-Hyuk Kweon
Neurotransmitters are released within a millisecond after Ca(2+) arrives at an active zone. However, the vesicle fusion pathway underlying this synchronous release is yet to be understood. At the center of controversy is whether hemifusion, in which outer leaflets are merged while inner leaflets are still separated, is an on-pathway or off-pathway product of Ca(2+)-triggered exocytosis. Using the single vesicle fusion assay, we recently demonstrated that hemifusion is an on-pathway intermediate that immediately proceeds to full fusion upon Ca(2+) triggering...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28408866/post-translational-modifications-and-protein-quality-control-in-motor-neuron-and-polyglutamine-diseases
#13
REVIEW
Fabio Sambataro, Maria Pennuto
Neurodegenerative diseases, including motor neuron and polyglutamine (polyQ) diseases, are a broad class of neurological disorders. These diseases are characterized by neuronal dysfunction and death, and by the accumulation of toxic aggregation-prone proteins in the forms of inclusions and micro-aggregates. Protein quality control is a cellular mechanism to reduce the burden of accumulation of misfolded proteins, a function that results from the coordinated actions of chaperones and degradation systems, such as the ubiquitin-proteasome system (UPS) and autophagy-lysosomal degradation system...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28396624/granulostasis-protein-quality-control-of-rnp-granules
#14
REVIEW
Simon Alberti, Daniel Mateju, Laura Mediani, Serena Carra
Ribonucleoprotein (RNP) granules transport, store, or degrade messenger RNAs, thereby indirectly regulating protein synthesis. Normally, RNP granules are highly dynamic compartments. However, because of aging or severe environmental stress, RNP granules, in particular stress granules (SGs), convert into solid, aggregate-like inclusions. There is increasing evidence that such RNA-protein inclusions are associated with several age-related neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), fronto-temporal dementia (FTD) and Alzheimer's disease (AD)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28386218/control-of-mrna-translation-in-als-proteinopathy
#15
REVIEW
Gianluca Cestra, Simona Rossi, Michela Di Salvio, Mauro Cozzolino
Cells robustly reprogram gene expression during stress generated by protein misfolding and aggregation. In this condition, cells assemble the bulk of mRNAs into translationally silent stress granules (SGs), while they sustain the translation of specific mRNAs coding for proteins that are needed to overcome cellular stress. Alterations of this process are deeply associated to neurodegeneration. This is the case of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder caused by a selective loss of motor neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28386217/genome-wide-association-study-gwas-between-attention-deficit-hyperactivity-disorder-adhd-and-obsessive-compulsive-disorder-ocd
#16
McKenzie L Ritter, Wei Guo, Jack F Samuels, Ying Wang, Paul S Nestadt, Janice Krasnow, Benjamin D Greenberg, Abby J Fyer, James T McCracken, Daniel A Geller, Dennis L Murphy, James A Knowles, Marco A Grados, Mark A Riddle, Steven A Rasmussen, Nicole C McLaughlin, Erika L Nurmi, Kathleen D Askland, Bernadette Cullen, John Piacentini, David L Pauls, Joseph Bienvenu, Evelyn Stewart, Fernando S Goes, Brion Maher, Ann E Pulver, Manuel Mattheisen, Ji Qian, Gerald Nestadt, Yin Yao Shugart
Objective: The aim of this study was to identify any potential genetic overlap between attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). We hypothesized that since these disorders share a sub-phenotype, they may share common risk alleles. In this manuscript, we report the overlap found between these two disorders. Methods: A meta-analysis was conducted between ADHD and OCD, and polygenic risk scores (PRS) were calculated for both disorders. In addition, a protein-protein analysis was completed in order to examine the interactions between proteins; p-values for the protein-protein interaction analysis was calculated using permutation...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28386216/calpastatin-overexpression-preserves-cognitive-function-following-seizures-while-maintaining-post-injury-neurogenesis
#17
Vanessa M Machado, Ana Sofia Lourenço, Cláudia Florindo, Raquel Fernandes, Caetana M Carvalho, Inês M Araújo
In the adult mammalian brain, new neurons continue to be produced throughout life in two main regions in the brain, the subgranular zone (SGZ) in the hippocampus and the subventricular zone in the walls of the lateral ventricles. Neural stem cells (NSCs) proliferate in these niches, and migrate as neuroblasts, to further differentiate in locations where new neurons are needed, either in normal or pathological conditions. However, the endogenous attempt of brain repair is not very efficient. Calpains are proteases known to be involved in neuronal damage and in cell proliferation, migration and differentiation of several cell types, though their effects on neurogenesis are not well known...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28381988/increased-excitatory-synaptic-transmission-of-dentate-granule-neurons-in-mice-lacking-psd-95-interacting-adhesion-molecule-neph2-kirrel3-during-the-early-postnatal-period
#18
Junyeop D Roh, Su-Yeon Choi, Yi Sul Cho, Tae-Yong Choi, Jong-Sil Park, Tyler Cutforth, Woosuk Chung, Hanwool Park, Dongsoo Lee, Myeong-Heui Kim, Yeunkum Lee, Seojung Mo, Jeong-Seop Rhee, Hyun Kim, Jaewon Ko, Se-Young Choi, Yong Chul Bae, Kang Shen, Eunjoon Kim, Kihoon Han
Copy number variants and point mutations of NEPH2 (also called KIRREL3) gene encoding an immunoglobulin (Ig) superfamily adhesion molecule have been linked to autism spectrum disorders, intellectual disability and neurocognitive delay associated with Jacobsen syndrome, but the physiological roles of Neph2 in the mammalian brain remain largely unknown. Neph2 is highly expressed in the dentate granule (DG) neurons of the hippocampus and is localized in both dendrites and axons. It was recently shown that Neph2 is required for the formation of mossy fiber filopodia, the axon terminal structure of DG neurons forming synapses with GABAergic neurons of CA3...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28381987/the-ubiquitination-disaggregation-and-proteasomal-degradation-machineries-in-polyglutamine-disease
#19
REVIEW
Samir R Nath, Andrew P Lieberman
Polyglutamine disorders are chronic, progressive neurodegenerative diseases caused by expansion of a glutamine tract in widely expressed genes. Despite excellent models of disease, a well-documented clinical history and progression, and established genetic causes, there are no FDA approved, disease modifying treatments for these disorders. Downstream of the mutant protein, several divergent pathways of toxicity have been identified over the last several decades, supporting the idea that targeting only one of these pathways of toxicity is unlikely to robustly alleviate disease progression...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28377693/inhibition-of-mammalian-target-of-rapamycin-mtor-signaling-in-the-insular-cortex-alleviates-neuropathic-pain-after-peripheral-nerve-injury
#20
Minjee Kwon, Jeongsoo Han, Un Jeng Kim, Myeounghoon Cha, Sun Woo Um, Sun Joon Bai, Seong-Karp Hong, Bae Hwan Lee
Injury of peripheral nerves can trigger neuropathic pain, producing allodynia and hyperalgesia via peripheral and central sensitization. Recent studies have focused on the role of the insular cortex (IC) in neuropathic pain. Because the IC is thought to store pain-related memories, translational regulation in this structure may reveal novel targets for controlling chronic pain. Signaling via mammalian target of rapamycin (mTOR), which is known to control mRNA translation and influence synaptic plasticity, has been studied at the spinal level in neuropathic pain, but its role in the IC under these conditions remains elusive...
2017: Frontiers in Molecular Neuroscience
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