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https://www.readbyqxmd.com/read/28212525/ablation-of-ferroptosis-regulator-glutathione-peroxidase-4-in-forebrain-neurons-promotes-cognitive-impairment-and-neurodegeneration
#1
William Sealy Hambright, Rene Solano Fonseca, Liuji Chen, Ren Na, Qitao Ran
Synaptic loss and neuron death are the underlying cause of neurodegenerative diseases such as Alzheimer's disease (AD); however, the modalities of cell death in those diseases remain unclear. Ferroptosis, a newly identified oxidative cell death mechanism triggered by massive lipid peroxidation, is implicated in the degeneration of neurons populations such as spinal motor neurons and midbrain neurons. Here, we investigated whether neurons in forebrain regions (cerebral cortex and hippocampus) that are severely afflicted in AD patients might be vulnerable to ferroptosis...
February 1, 2017: Redox Biology
https://www.readbyqxmd.com/read/28198092/the-burden-of-neurological-disease-in-the-united-states-a-summary-report-and-call-to-action
#2
EDITORIAL
Clifton L Gooch, Etienne Pracht, Amy R Borenstein
: The United States carries a substantial fiscal burden resulting from the nearly 100 million Americans with neurological disease. The combined annual costs of Alzheimer's and other dementias, low back pain, stroke, traumatic brain injury, migraine, epilepsy, multiple sclerosis, spinal cord injury and Parkinson's disease totals nearly 800 billion dollars and is rapidly rising due to the aging of the U.S. POPULATION: We provide a summary overview of the substantial current and future economic impact of neurological disease, and provide an action plan for reducing this burden through neurological research and enhanced clinical management of neurological disorders in the United States...
February 15, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28131209/potential-oxidative-stress-biomarkers-of-mild-cognitive-impairment-due-to-alzheimer-disease
#3
REVIEW
Ana García-Blanco, Miguel Baquero, Máximo Vento, Esperanza Gil, Luis Bataller, Consuelo Cháfer-Pericás
The high and increasing incidence of Alzheimer Disease (AD) worldwide is a major global concern. Classical diagnosis is carried out in the dementia phase, often in the moderate stages when treatment efficacy is limited. Nowadays, early diagnosis, even in pre-dementia stages, is possible in selected cases within an appropriate clinical setting, employing cerebral spinal fluid (CSF) sample analysis and neuroimaging procedures. In spite of the accurate diagnosis achieved by novel CSF biomarkers or positron emission tomography beta-amyloid tracers, these tests are invasive and expensive...
February 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28123067/tau-reduction-prevents-neuronal-loss-and-reverses-pathological-tau-deposition-and-seeding-in-mice-with-tauopathy
#4
Sarah L DeVos, Rebecca L Miller, Kathleen M Schoch, Brandon B Holmes, Carey S Kebodeaux, Amy J Wegener, Guo Chen, Tao Shen, Hien Tran, Brandon Nichols, Tom A Zanardi, Holly B Kordasiewicz, Eric E Swayze, C Frank Bennett, Marc I Diamond, Timothy M Miller
Accumulation of hyperphosphorylated tau directly correlates with cognitive decline in Alzheimer's disease and other primary tauopathies. One therapeutic strategy may be to reduce total tau expression. We identified antisense oligonucleotides (ASOs) that selectively decreased human tau mRNA and protein in mice expressing mutant P301S human tau. After reduction of human tau in this mouse model of tauopathy, fewer tau inclusions developed, and preexisting phosphorylated tau and Thioflavin S pathology were reversed...
January 25, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28095679/non-naturally-occurring-small-molecule-microtubule-stabilizing-agents-a-potential-tactic-for-cns-directed-therapies
#5
REVIEW
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...
18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28063055/isolation-of-microglia-and-immune-infiltrates-from-mouse-and-primate-central-nervous-system
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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/27890382/-alzheimer-s-disease-cerebro-spinal-fluid-biomarkers-a-clinical-research-tool-sometimes-useful-in-daily-clinical-practice-of-memory-clinics-for-the-diagnosis-of-complex-cases
#17
E Magnin, J Dumurgier, E Bouaziz-Amar, S Bombois, D Wallon, A Gabelle, S Lehmann, F Blanc, O Bousiges, D Hannequin, B Jung, C Miguet-Alfonsi, M Quillard, F Pasquier, K Peoc'h, J-L Laplanche, J Hugon, C Paquet
The role of biomarkers in clinical research was recently highlighted in the new criteria for the diagnosis of Alzheimer's disease. Cerebro-spinal fluid (CSF) biomarkers (total Tau protein, threonine 181 phosphorylated Tau protein and amyloid Aβ1-42 peptide) are associated with cerebral neuropathological lesions observed in Alzheimer's disease (neuronal death, neurofibrillary tangle with abnormal Tau deposits and amyloid plaque). Aβ1-40 amyloid peptide dosage helps to interpret Aβ1-42 results. As suggested in the latest international criteria and the French HAS (Haute Autorité de santé) recommendations, using theses CSF biomarkers should not be systematic but sometimes could be performed to improve confidence about the diagnostic of Alzheimer's disease in young subjects or in complex clinical situations...
November 24, 2016: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/27866120/evidence-based-guidelines-on-the-therapeutic-use-of-transcranial-direct-current-stimulation-tdcs
#18
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/27798193/trem2-dap12-signal-elicits-proinflammatory-response-in-microglia-and-exacerbates-neuropathic-pain
#19
Masaaki Kobayashi, Hiroyuki Konishi, Akira Sayo, Toshiyuki Takai, Hiroshi Kiyama
: Neuropathic pain afflicts millions of people, and the development of an effective treatment for this intractable pain is an urgent issue. Recent evidence has implicated microglia in neuropathic pain. The present study showed that the DNAX-activating protein of 12 kDa (DAP12) and its associated "triggering receptor expressed on myeloid cells 2" (TREM2) were predominantly expressed by microglia in the dorsal horn after spinal nerve injury, revealing a role for TREM2/DAP12 signaling in neuropathic pain...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27714554/intrinsic-functional-connectivity-alterations-in-cognitively-intact-elderly-apoe-%C3%AE%C2%B54-carriers-measured-by-eigenvector-centrality-mapping-are-related-to-cognition-and-csf-biomarkers-a-preliminary-study
#20
Xiao Luo, Tiantian Qiu, Yunlu Jia, Peiyu Huang, Xiaojun Xu, Xinfeng Yu, Zhujing Shen, Yerfan Jiaerken, Xiaojun Guan, Jiong Zhou, Minming Zhang
Apolipoprotein E (APOE) ε4 allele is the best established genetic risk factor for sporadic Alzheimer's disease (AD). However, there is a need to understand the effects of this genotype on the brain by simultaneously assessing intrinsic brain network and cerebral spinal fluid (CSF) biomarkers changes in healthy older ε4 carriers. Thirteen cognitively intact, elderly APOE ε4 carriers and 22 ε3 homozygotes were included in the present study. Eigenvector centrality mapping (ECM) was used to identify brain network hub organization based on resting-state functional MRI (rsfMRI)...
October 6, 2016: Brain Imaging and Behavior
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