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https://www.readbyqxmd.com/read/28095679/non-naturally-occurring-small-molecule-microtubule-stabilizing-agents-a-potential-tactic-for-cns-directed-therapies
#1
Carlo Ballatore, Kurt R Brunden, John Q Trojanowski, Virginia M-Y Lee, Amos B Smith
Several independent studies indicate that microtubule (MT)-stabilizing agents hold considerable promise as candidate therapeutics for a wide spectrum of conditions of the central nervous system (CNS), from brain tumors to spinal cord injury, as well as a number of neurodegenerative diseases, including Alzheimer's disease, frontotemporal lobar degeneration, Parkinson's disease, and amyotrophic lateral sclerosis. Although the identification and development of candidate compounds for CNS-directed MT-stabilizing therapies has been a challenge in drug discovery for many years, a growing number of molecules have now been identified that exhibit both MT-stabilizing activity and brain penetration...
January 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28063055/isolation-of-microglia-and-immune-infiltrates-from-mouse-and-primate-central-nervous-system
#2
Thais F Galatro, Ilia D Vainchtein, Nieske Brouwer, Erik W G M Boddeke, Bart J L Eggen
Microglia are the innate immune cells of the central nervous system (CNS) and play an important role in the maintenance of tissue homeostasis, providing neural support and neuroprotection. Microglia constantly survey their environment and quickly respond to homeostatic perturbations. Microglia are increasingly implicated in neuropathological and neurodegenerative conditions, such as Alzheimer's disease, Parkinson's disease, and glioma progression. Here, we describe a detailed isolation protocol for microglia and immune infiltrates, optimized for large amounts of post mortem tissue from human and rhesus macaque, as well as smaller tissue amounts from mouse brain and spinal cord, that yield a highly purified microglia population (up to 98 % purity)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28019127/astroglial-transcriptome-dysregulation-in-early-disease-of-an-als-mutant-sod1-mouse-model
#3
Sean J Miller, Ping-Wu Zhang, Jenna Glatzer, Jeffrey D Rothstein
Astroglia are a morphologically diverse and highly abundant cell type in the CNS. Despite these obvious observations, astroglia still remain largely uncharacterized at the cellular and molecular level. In disease contexts such as amyotrophic lateral sclerosis (ALS), it has been widely shown that astroglia downregulate crucial physiological functions, become hypertrophied, reactive, and toxic to motor neurons. However, little is known about the astroglia-specific transcriptomic changes that occur during ALS disease progression, especially early in disease...
December 25, 2016: Journal of Neurogenetics
https://www.readbyqxmd.com/read/28008944/amyloid-precursor-protein-modulates-nav1-6-sodium-channel-currents-through-a-go-coupled-jnk-pathway
#4
Shao Li, Xi Wang, Quan-Hong Ma, Wu-Lin Yang, Xiao-Gang Zhang, Gavin S Dawe, Zhi-Cheng Xiao
Amyloid precursor protein (APP), commonly associated with Alzheimer's disease, also marks axonal degeneration. In the recent studies, we demonstrated that APP aggregated at nodes of Ranvier (NORs) in myelinated central nervous system (CNS) axons and interacted with Nav1.6. However, the physiological function of APP remains unknown. In this study, we described reduced sodium current densities in APP knockout hippocampal neurons. Coexpression of APP or its intracellular domains containing a VTPEER motif with Nav1...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27989140/enolate-forming-compounds-as-a-novel-approach-to-cytoprotection
#5
Richard M LoPachin, Brian C Geohagen, Lars Ulrik Nordstrøm, Terrence Gavin
Evidence from laboratory studies and clinical trials suggests that plant-derived polyphenolic compounds such as curcumin, resveratrol, or phloretin might be useful in the treatment of certain diseases (e.g., Alzheimer's disease) and acute tissue injury states (e.g., spinal cord trauma). However, despite this potential, the corresponding chemical instability, toxic potential, and low bioavailability of these compounds could limit their ultimate clinical relevance. We have shown that pharmacophores of curcumin (e...
December 19, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27981499/direct-conversion-of-somatic-cells-into-induced-neurons
#6
REVIEW
Na An, Huiming Xu, Wei-Qiang Gao, Hao Yang
The progressive loss and degeneration of neurons in the central nervous system (CNS), as a result of traumas or diseases including Alzheimer's, Parkinson's, Huntington's disease, stroke, and traumatic injury to the brain and spinal cord, can usually have devastating effects on quality of life. The current strategies available for treatments are described including drug delivery, surgery, electrical stimulation, and cell-based tissue engineering approaches. However, apart from cell-based therapy, other attempts are limited in improving clinical outcomes...
December 16, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27959284/the-proposed-use-of-cervical-spinal-cord-stimulation-for-the-treatment-and-prevention-of-cognitive-decline-in-dementias-and-neurodegenerative-disorders
#7
Nestor D Tomycz
Cervical spinal cord stimulation is a well-established treatment for intractable neuropathic upper extremity pain. More than 20years ago it was demonstrated that cervical spinal cord stimulation could engender an increase in cerebral blood flow. Cerebral blood flow has been shown to be decreased in many patients with dementia and in various neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Furthermore, there is evidence that reduced cerebral blood flow worsens neurodegenerative disease and may also predict which patients progress from mild cognitive impairment to full blown Alzheimer's disease...
November 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27957611/barrier-function-in-the-peripheral-and-central-nervous-system-a-review
#8
REVIEW
A K Reinhold, H L Rittner
The peripheral (PNS) and central nervous system (CNS) are delicate structures, highly sensitive to homeostatic changes-and crucial for basic vital functions. Thus, a selection of barriers ensures the protection of the nervous system from noxious blood-borne or surrounding stimuli. In this chapter, anatomy and functioning of the blood-nerve (BNB), the blood-brain (BBB), and the blood-spinal cord barriers (BSCB) are presented and the key tight junction (TJ) proteins described: claudin-1, claudin-3, claudin-5, claudin-11, claudin-12, claudin-19, occludin, Zona occludens-1 (ZO-1), and tricellulin are by now identified as relevant for nerval barriers...
January 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27941618/aquaporins-in-the-spinal-cord
#9
REVIEW
Michal K Oklinski, Mariusz T Skowronski, Agnieszka Skowronska, Michael Rützler, Kirsten Nørgaard, John D Nieland, Tae-Hwan Kwon, Søren Nielsen
Aquaporins (AQPs) are water channel proteins robustly expressed in the central nervous system (CNS). A number of previous studies described the cellular expression sites and investigated their major roles and function in the brain and spinal cord. Among thirteen different mammalian AQPs, AQP1 and AQP4 have been mainly studied in the CNS and evidence has been presented that they play important roles in the pathogenesis of CNS injury, edema and multiple diseases such as multiple sclerosis, neuromyelitis optica spectrum disorders, amyotrophic lateral sclerosis, glioblastoma multiforme, Alzheimer's disease and Parkinson's disease...
December 7, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916623/multiple-beneficial-effects-of-melanocortin-mc4-receptor-agonists-in-experimental-neurodegenerative-disorders-therapeutic-perspectives
#10
REVIEW
Daniela Giuliani, Alessandra Ottani, Laura Neri, Davide Zaffe, Paolo Grieco, Jerzy Jochem, Gian Maria Cavallini, Anna Catania, Salvatore Guarini
Melanocortin peptides induce neuroprotection in acute and chronic experimental neurodegenerative conditions. Melanocortins likewise counteract systemic responses to brain injuries. Furthermore, they promote neurogenesis by activating critical signaling pathways. Melanocortin-induced long-lasting improvement in synaptic activity and neurological performance, including learning and memory, sensory-motor orientation and coordinated limb use, has been consistently observed in experimental models of acute and chronic neurodegeneration...
December 1, 2016: Progress in Neurobiology
https://www.readbyqxmd.com/read/27911749/casting-a-wide-net-role-of-perineuronal-nets-in-neural-plasticity
#11
Barbara A Sorg, Sabina Berretta, Jordan M Blacktop, James W Fawcett, Hiroshi Kitagawa, Jessica C F Kwok, Marta Miquel
Perineuronal nets (PNNs) are unique extracellular matrix structures that wrap around certain neurons in the CNS during development and control plasticity in the adult CNS. They appear to contribute to a wide range of diseases/disorders of the brain, are involved in recovery from spinal cord injury, and are altered during aging, learning and memory, and after exposure to drugs of abuse. Here the focus is on how a major component of PNNs, chondroitin sulfate proteoglycans, control plasticity, and on the role of PNNs in memory in normal aging, in a tauopathy model of Alzheimer's disease, and in drug addiction...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27911071/severe-brain-injury-in-massachusetts-assessing-the-continuum-of-care
#12
Laura Lorenz, Gabrielle Katz
Acquired brain injury (ABI) is a major public health problem in Massachusetts (Hackman et al, 2014) and includes traumatic brain injury (TBI), stroke, ABI-related infectious diseases, metabolic disorders affecting the central nervous system (brain and spinal cord), and brain tumor. Advances in emergency medical care and neurosurgery mean that more people are surviving severe traumatic brain injury (Trexler et al, 2014). Yet many patients with severe TBI in particular, are not receiving inpatient services after initial treatment (Hackman et al, 2014; CDC, 2014) or later that are known to be effective (Malec & Kean, 2015; Lewis & Horn, 2015; BI Commission, 2011; Kolakowsky-Hayner et al, 2000; Interviews)...
December 10, 2015: Issue Brief
https://www.readbyqxmd.com/read/27866120/evidence-based-guidelines-on-the-therapeutic-use-of-transcranial-direct-current-stimulation-tdcs
#13
REVIEW
Jean-Pascal Lefaucheur, Andrea Antal, Samar S Ayache, David H Benninger, Jérôme Brunelin, Filippo Cogiamanian, Maria Cotelli, Dirk De Ridder, Roberta Ferrucci, Berthold Langguth, Paola Marangolo, Veit Mylius, Michael A Nitsche, Frank Padberg, Ulrich Palm, Emmanuel Poulet, Alberto Priori, Simone Rossi, Martin Schecklmann, Sven Vanneste, Ulf Ziemann, Luis Garcia-Larrea, Walter Paulus
A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson's disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer's disease, tinnitus, depression, schizophrenia, and craving/addiction...
January 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/27699087/guanosine-a-neuromodulator-with-therapeutic-potential-in-brain-disorders
#14
REVIEW
Débora Lanznaster, Tharine Dal-Cim, Tetsadê C B Piermartiri, Carla I Tasca
Guanosine is a purine nucleoside with important functions in cell metabolism and a protective role in response to degenerative diseases or injury. The past decade has seen major advances in identifying the modulatory role of extracellular action of guanosine in the central nervous system (CNS). Evidence from rodent and cell models show a number of neurotrophic and neuroprotective effects of guanosine preventing deleterious consequences of seizures, spinal cord injury, pain, mood disorders and aging-related diseases, such as ischemia, Parkinson's and Alzheimer's diseases...
October 2016: Aging and Disease
https://www.readbyqxmd.com/read/27678294/protective-roles-of-slc30a3-against-endoplasmic-reticulum-stress-via-erk1-2-activation
#15
Hisaka Kurita, Rika Okuda, Kazuki Yokoo, Masatoshi Inden, Isao Hozumi
Endoplasmic reticulum (ER) stress has been thought to be involved to neurodegenerative diseases such as Alzheimer's disease (AD) or Amyotrophic lateral sclerosis (ALS). The previous studies have shown that SLC30A3 level is decreased in prefrontal cortex of AD patients. In addition, we have shown that level of zinc (Zn) is increased in cerebrospinal fluid and SLC30A3 level is decreased in spinal cord of ALS patients. It was thought that both SLC30A3 and ER stress could be related to the cause of AD and ALS, however the relationship between ER stress and SLC30A3 has not been elucidated...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27553276/calcium-s-role-as-nuanced-modulator-of-cellular-physiology-in-the-brain
#16
Hilaree N Frazier, Shaniya Maimaiti, Katie L Anderson, Lawrence D Brewer, John C Gant, Nada M Porter, Olivier Thibault
Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer's disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration...
August 20, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27549144/role-of-kca3-1-channels-in-cns-diseases-a-concise-review
#17
Sinoy Sugunan, Sreekala S Nampoothiri, Tanya Garg, Rajanikant G Krishnamurthy
KCa3.1 protein is part of a heterotetrameric voltage-independent potassium channel, the activity of which depends on the intracellular calcium binding to calmodulin. KCa3.1 is immensely significant in regulating immune responses and primarily expressed in cells of hematopoietic lineage. It is one of the attractive pharmacological targets that are known to inhibit neuroinflammation. KCa3.1 blockers mediate neuroprotection through multiple mechanisms, such as by targeting microglia-mediated neuronal killing. KCa3...
August 22, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27546055/the-choroid-plexus-in-health-and-in-disease-dialogues-into-and-out-of-the-brain
#18
Fernanda Marques, João Carlos Sousa, Alexandra Brito, Jens Pahnke, Cecilia Santos, Margarida Correia-Neves, Joana Almeida Palha
This article brings the choroid plexus into the context of health and disease. It is remarkable that the choroid plexus, composed by the monolayer of epithelial cells that lie in a highly vascularized stroma, floating within the brain ventricles, gets so little attention in major physiology and medicine text books and in the scientific literature in general. Consider that it is responsible for producing most of the about 150mL of cerebrospinal fluid that fills the brain ventricles and the subarachnoid space and surrounds the spinal cord in the adult human brain, which is renewed approximately 2-3 times daily...
August 18, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27540523/the-evaluation-of-nerve-growth-factor-over-expression-on-neural-lineage-specific-genes-in-human-mesenchymal-stem-cells
#19
Yousef Mortazavi, Fatemeh Sheikhsaran, Gholamreza Khamisipour Khamisipour, Masoud Soleimani, Ali Teimuri, Somayeh Shokri
OBJECTIVE: Treatment and repair of neurodegenerative diseases such as brain tumors, spinal cord injuries, and functional disorders, including Alzheimer's disease, are challenging problems. A common treatment approach for such disorders involves the use of mesenchymal stem cells (MSCs) as an alternative cell source to replace injured cells. However, use of these cells in hosts may potentially cause adverse outcomes such as tumorigenesis and uncontrolled differentiation. In attempt to generate mesenchymal derived neural cells, we have infected MSCs with recombinant lentiviruses that expressed nerve growth factor (NGF) and assessed their neural lineage genes...
July 2016: Cell Journal
https://www.readbyqxmd.com/read/27539630/risk-of-dementia-in-patients-with-spinal-cord-injury-a-nationwide-population-based-cohort-study
#20
ShihWei Huang, WeiTe Wang, LinChuan Chou, TsanHon Liou, Hui-Wen Lin
Spinal cord injury (SCI) can cause physical disability and psychological distress; however, whether SCI is a risk factor for dementia is unclear. This study evaluated the incidence of dementia in patients with SCI. Study participants were recruited from a nationwide cohort during 2004-2007 and categorized into SCI (patients diagnosed with SCI; n = 941) and non-SCI (age- and sex-matched controls; n = 5,060) cohorts. Each participant was followed for 7 years until diagnosis of dementia or December 31, 2010, whichever occurred first...
August 18, 2016: Journal of Neurotrauma
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