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https://www.readbyqxmd.com/read/28819074/-molecular-pathogenesis-of-polyglutamine-diseases
#1
Yuji Takahashi
Polyglutamine diseases result from gain-of-function mutations. The expanded polyglutamine tracts lead to conformational changes in proteins, resulting in their aggregation. The intermediates including monomers or oligomers, are more toxic than the aggregates to neurons. At the molecular level, protein misfolding, transcriptional dysregulation, deranged calcium homeostasis, impaired cytoskeleton/axonal transport, mitochondrial dysfunction, and RNA toxicity contribute to disease progression. Understanding the underlying pathogenesis facilitates development of therapy for polyglutamine diseases...
August 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28818525/whole-transcriptome-microarray-analysis-reveals-regulation-of-rab4-by-rbm5-in-neurons
#2
Travis C Jackson, Shawn E Kotermanski, Patrick M Kochanek
RNA binding motif 5 (RBM5) is a nuclear protein that modulates gene transcription and mRNA splicing in cancer cells. The brain is among the highest RBM5 expressing organ in the body but its mRNA target(s) or functions in the CNS have not been elucidated. Here we knocked down (KO) RBM5 in primary rat cortical neurons and analyzed total RNA extracts by gene microarray vs. neurons transduced with lentivirus to deliver control (non-targeting) shRNA. The mRNA levels of Sec23A (involved in ER-Golgi transport) and the small GTPase Rab4a (involved in endocytosis/protein trafficking) were increased in RBM5 KO neurons relative to controls...
August 14, 2017: Neuroscience
https://www.readbyqxmd.com/read/28816642/proteomic-analysis-of-the-human-olfactory-bulb
#3
Manjunath Dammalli, Gourav Dey, Anil K Madugundu, Manish Kumar, Benvil Rodrigues, Harsha Gowda, Bychapur Gowrishankar Siddaiah, Anita Mahadevan, Susarla Krishna Shankar, Thottethodi Subrahmanya Keshava Prasad
The importance of olfaction to human health and disease is often underappreciated. Olfactory dysfunction has been reported in association with a host of common complex diseases, including neurological diseases such as Alzheimer's disease and Parkinson's disease. For health, olfaction or the sense of smell is also important for most mammals, for optimal engagement with their environment. Indeed, animals have developed sophisticated olfactory systems to detect and interpret the rich information presented to them to assist in day-to-day activities such as locating food sources, differentiating food from poisons, identifying mates, promoting reproduction, avoiding predators, and averting death...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28812939/removing-dysfunctional-mitochondria-from-axons-independent-of-mitophagy-under-pathophysiological-conditions
#4
Mei-Yao Lin, Xiu-Tang Cheng, Yuxiang Xie, Qian Cai, Zu-Hang Sheng
Chronic mitochondrial dysfunction has been implicated in major neurodegenerative diseases. Long-term cumulative pathological stress leads to axonal accumulation of damaged mitochondria. Therefore, the early removal of defective mitochondria from axons constitutes a critical step of mitochondrial quality control. We recently investigated the axonal mitochondrial response to mild stress in wild-type neurons and chronic mitochondrial defects in amyotrophic lateral sclerosis (ALS)- and Alzheimer disease (AD)-linked neurons...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28811263/the-role-of-escrt-during-development-and-functioning-of-the-nervous-system
#5
REVIEW
Rémy Sadoul, Marine H Laporte, Romain Chassefeyre, Yves Goldberg, Christine Chatellard, Fiona J Hemming, Sandrine Fraboulet
The endosomal sorting complex required for transport (ESCRT) is made of subcomplexes (ESCRT I-III), crucial to membrane remodelling at endosomes, nuclear envelope and cell surface. ESCRT-III shapes membranes and in most cases cooperates with the ATPase VPS4 to mediate fission of membrane necks from the inside. The first ESCRT complexes mainly serve to catalyse the formation of ESCRT-III but can be bypassed by accessory proteins like the Alg-2 interacting protein-X (ALIX). In the nervous system, ALIX/ESCRT controls the survival of embryonic neural progenitors and later on the outgrowth and pruning of axons and dendrites, all necessary steps to establish a functional brain...
August 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28808087/the-drosophila-lc8-homologue-cut-up-specifies-the-axonal-transport-of-proteasomes
#6
Tabita Kreko-Pierce, Benjamin A Eaton
Because of their functional polarity and elongated morphologies, microtubule-based transport of proteins and organelles is critical for normal neuronal function. The proteasome is required throughout the neuron for the highly regulated degradation of a broad set of protein targets whose functions underlie key physiological responses including synaptic plasticity and axonal degeneration. Molecularly, the relationship between proteasome transport and the transport of the targets of proteasomes is unclear. The dynein motor complex is required for the microtubule-based motility of numerous proteins and organelles in neurons...
August 14, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28806498/pacinian-corpuscles-in-human-lymph-nodes
#7
J Feito, J L Cobo, A Santos-Briz, J A Vega
The occurrence of Pacinian corpuscles associated to lymph nodes is an anatomical rarity and very scarce information exists in this regard. Here we examined immunohistochemically four Pacinian corpuscles found in the close vicinity of the hiliar blood vessels of lymph nodes (2 cervical, 1 axillary, and 1 inguinal) during routine surgical pathology. Pacinian corpuscles were normally arranged and displayed a pattern of protein distribution as follows: the axon was positive for neurofilament proteins and neuron specific enolase, the inner core cells showed intense S100 protein and vimentin immunostaining while they were negative for glial fibrillary acidic protein, type IV collagen and glucose transporter 1; vimentin, type IV collagen, and glucose transporter 1 were also observed also in the outer-core and the capsule...
August 14, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28803831/localization-of-connexin-43-gap-junctions-and-hemichannels-in-tanycytes-of-adult-mice
#8
Anett Szilvásy-Szabó, Edina Varga, Zsuzsa Beliczai, Ronald M Lechan, Csaba Fekete
Tanycytes are specialized glial cells lining the lateral walls and the floor of the third ventricle behind the optic chiasm. In addition to functioning as barrier cells, they also have an important role in the regulation of neuroendocrine axes and energy homeostasis. To determine whether tanycytes communicate with each other via Connexin 43 (Cx43) gap junctions, individual tanycytes were loaded with Lucifer yellow (LY) through a patch pipette. In all cases, LY filled a larger group of tanycytes as well as blood vessels adjacent to tanycyte processes...
August 10, 2017: Brain Research
https://www.readbyqxmd.com/read/28803760/mechanism-of-action-of-botulinum-neurotoxin-unexpected-consequences
#9
REVIEW
Mark Hallett
Botulinum neurotoxin (BoNT) is a widely used therapeutic in part because its mechanism of action is much wider than initially expected. Since BoNT is taken up more avidly in active presynaptic terminals, there is some selectivity for weakening muscles involved in frequent involuntary movements. BoNT blocks gamma motoneurons as well as alpha motoneurons, hence reducing afferent spindle activity which appears to have a favorable effect. Some BoNT is retrogradely transported in the motor axons, leading at least to reduction in recurrent inhibition mediated by the Renshaw cell...
August 10, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28798098/erratum-for-duraine-et-al-herpes-simplex-virus-ge-gi-and-us9-promote-both-envelopment-and-sorting-of-virus-particles-in-the-cytoplasm-of-neurons-two-processes-that-precede-anterograde-transport-in-axons
#10
Grayson DuRaine, Todd W Wisner, Paul Howard, Melissa Williams, David C Johnson
No abstract text is available yet for this article.
September 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28774322/tau-accumulation-in-the-retina-promotes-early-neuronal-dysfunction-and-precedes-brain-pathology-in-a-mouse-model-of-alzheimer-s-disease
#11
Marius Chiasseu, Luis Alarcon-Martinez, Nicolas Belforte, Heberto Quintero, Florence Dotigny, Laurie Destroismaisons, Christine Vande Velde, Fany Panayi, Caroline Louis, Adriana Di Polo
BACKGROUND: Tau is an axon-enriched protein that binds to and stabilizes microtubules, and hence plays a crucial role in neuronal function. In Alzheimer's disease (AD), pathological tau accumulation correlates with cognitive decline. Substantial visual deficits are found in individuals affected by AD including a preferential loss of retinal ganglion cells (RGCs), the neurons that convey visual information from the retina to the brain. At present, however, the mechanisms that underlie vision changes in these patients are poorly understood...
August 3, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28770630/axonal-transport-proteins-as-biomarkers-of-neurodegeneration
#12
Kelly Hares, Alastair Wilkins
No abstract text is available yet for this article.
August 3, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/28768837/vitamin-d-in-the-spectrum-of-prediabetes-and-cardiovascular-autonomic-dysfunction
#13
REVIEW
Rumyana Dimova, Tsvetalina Tankova, Nevena Chakarova
Vitamin D is a fat-soluble secosteroid hormone with pleiotropic effects. 1,25-Dihydroxyvitamin D coordinates the biosynthesis of neurotransmitters in the central nervous system, which regulate cardiovascular autonomic function and may explain its putative role in the development of cardiovascular autonomic neuropathy (CAN). CAN is an independent risk factor for mortality in patients with diabetes and prediabetes and is associated with an increased risk of developing type 2 diabetes and cardiovascular disease...
August 2, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28758946/hippocampal-proteome-of-rats-subjected-to-the-li-pilocarpine-epilepsy-model-and-the-effect-of-carisbamate-treatment
#14
José Eduardo Marques-Carneiro, Daniele Suzete Persike, Julia Julie Litzahn, Jean-Christophe Cassel, Astrid Nehlig, Maria José da Silva Fernandes
In adult rats, the administration of lithium-pilocarpine (LiPilo) reproduces most clinical and neuropathological features of human temporal lobe epilepsy (TLE). Carisbamate (CRS) possesses the property of modifying epileptogenesis in this model. Indeed, about 50% of rats subjected to LiPilo status epilepticus (SE) develop non-convulsive seizures (NCS) instead of motor seizures when treated with CRS. However, the mechanisms underlying these effects remain unknown. The aim of this study was to perform a proteomic analysis in the hippocampus of rats receiving LiPilo and developing motor seizures or NCS following CRS treatment...
July 30, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28754069/axonal-spheroids-in-ovine-neuroaxonal-dystrophy-are-immunopositive-to-kinesin-and-dynein
#15
John W Finnie, Jim Manavis
Neuroaxonal dystrophy (NAD) is a neurologic disorder of sheep characterized by accumulation of numerous axonal swellings (spheroids) in specific regions of the brainstem and spinal cord. Disruption of axonal transport, which is driven in anterograde and retrograde directions by the molecular motors, kinesin and dynein, respectively, is believed to contribute to spheroid development. Accordingly, we examined spheroids in ovine NAD cases immunohistochemically for kinesin and dynein and found both motor proteins, with dynein more strongly expressed than kinesin...
July 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28751858/distinct-localization-of-snap47-protein-in-gabaergic-and-glutamatergic-neurons-in-the-mouse-and-the-rat-hippocampus
#16
Agnieszka Münster-Wandowski, Heike Heilmann, Felix Bolduan, Thorsten Trimbuch, Yuchio Yanagawa, Imre Vida
Synaptosomal-associated protein of 47 kDa (SNAP47) isoform is an atypical member of the SNAP family, which does not contribute directly to exocytosis and synaptic vesicle (SV) recycling. Initial characterization of SNAP47 revealed a widespread expression in nervous tissue, but little is known about its cellular and subcellular localization in hippocampal neurons. Therefore, in the present study we applied multiple-immunofluorescence labeling, immuno-electron microscopy and in situ hybridization (ISH) and analyzed the localization of SNAP47 in pre- and postsynaptic compartments of glutamatergic and GABAergic neurons in the mouse and rat hippocampus...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28749471/pre-synaptic-trkb-in-basolateral-amygdala-neurons-mediates-bdnf-signaling-transmission-in-memory-extinction
#17
Yuan Li, Dongdong Wang, Yang Li, Hongxia Chu, Lining Zhang, Ming Hou, Xingyu Jiang, Zheyu Chen, Bo Su, Tao Sun
Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, TrkB, play an essential role in memory extinction. Our previous work has shown that JIP3 (JNK interacted protein 3) mediates anterograde axonal transport of TrkB through the direct binding of its coiled-coil domain 1 (CC1) with TrkB. Here, we constructed a fluorescent CC1 and enhanced green fluorescent protein (EGFP) fused protein, CC1-EGFP, and found that CC1-EGFP could specifically interrupt TrkB anterograde axonal transport and its localization at the pre-synaptic site...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28743955/early-synaptic-dysfunction-induced-by-%C3%AE-synuclein-in-a-rat-model-of-parkinson-s-disease
#18
Jenny-Ann Phan, Kathrine Stokholm, Justyna Zareba-Paslawska, Steen Jakobsen, Kim Vang, Albert Gjedde, Anne M Landau, Marina Romero-Ramos
Evidence suggests that synapses are affected first in Parkinson's disease (PD). Here, we tested the claim that pathological accumulation of α-synuclein, and subsequent synaptic disruption, occur in absence of dopaminergic neuron loss in PD. We determined early synaptic changes in rats that overexpress human α-synuclein by local injection of viral-vectors in midbrain. We aimed to achieve α-synuclein levels sufficient to induce terminal pathology without significant loss of nigral neurons. We tested synaptic disruption in vivo by analyzing motor defects and binding of a positron emission tomography (PET) radioligand to the vesicular monoamine transporter 2, (VMAT2), [(11)C]dihydrotetrabenazine (DTBZ)...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28739532/denervated-muscle-fibers-induce-mitochondrial-peroxide-generation-in-neighboring-innervated-fibers-role-in-muscle-aging
#19
Natalie Pollock, Caroline A Staunton, Aphrodite Vasilaki, Anne McArdle, Malcolm J Jackson
Disruption of neuromuscular junctions and denervation of some muscle fibers occurs in ageing skeletal muscle and contribute to loss of muscle mass and function. Aging is associated with mitochondrial dysfunction and loss of redox homeostasis potentially occurs through increased mitochondrial generation of reactive oxygen species (ROS). No specific link between increased mitochondrial ROS generation and denervation has been defined in muscle ageing. To address this, we have examined the effect of experimental denervation of all fibers, or only a proportion of the fibers, in the mouse tibialis anterior (TA) muscle on muscle mitochondrial peroxide generation...
July 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28734834/dynein-binds-and-stimulates-axonal-motility-of-the-endosome-adaptor-and-neep21-family-member-calcyon
#20
Liang Shi, Nagendran Muthusamy, Deanna Smith, Clare Bergson
The neuron-enriched, endosomal protein Calcyon (Caly) regulates endocytosis and vesicle sorting, and is important for synaptic plasticity and brain development. In the current investigation of Caly interacting proteins in brain, the microtubule retrograde motor subunit, cytoplasmic dynein 1 heavy chain (DYNC1H), and microtubule structural proteins, α and β tubulin, were identified as Caly associated proteins by MALDI-ToF/ToF. Direct interaction of the Caly-C terminus with dynein and tubulin was further confirmed in in vitro studies...
July 19, 2017: International Journal of Biochemistry & Cell Biology
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