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https://www.readbyqxmd.com/read/28539884/the-analysis-of-two-bdnf-polymorphisms-g196a-c270t-in-chinese-sporadic-amyotrophic-lateral-sclerosis
#1
Lianping Xu, Danyang Tian, Jiao Li, Lu Chen, Lu Tang, Dongsheng Fan
Amyotrophic lateral sclerosis (ALS) is an ethnically heterogeneous motor neuron disease that results from the selective death of motor neurons in the brain and spinal cord. Brain-derived neurotrophic factor (BDNF) is widely distributed across the central and peripheral nervous systems and plays neurotrophic and other physiological roles in various brain regions. Alterations of neurotrophin availability have been proposed as a pathogenic mechanism underlying ALS neurodegeneration. Several genetic studies have shown a significant association between schizophrenia, Alzheimer's disease, and Parkinson's disease and certain BDNF polymorphisms, specifically G196A (rs6265) and C270T (rs56164415)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28526745/identification-and-characterisation-of-nanobodies-targeting-the-epha4-receptor
#2
Lies Schoonaert, Laura Rué, Bart Roucourt, Mieke Timmers, Susan Little, Lucía Chávez Gutiérrez, Maarten Dewilde, Peter Joyce, Adam Curnock, Peter Weber, Jurgen Haustraete, Gholamreza Hassanzadeh-Ghassabeh, Bart De Strooper, Ludo Van Den Bosch, Philip Van Damme, Robin Lemmens, Wim Robberecht
The ephrin receptor A4 (EphA4) is one of the receptors in the ephrin system that plays a pivotal role in a variety of cell-cell interactions, mostly studied during development. In addition, EphA4 has been found to play a role in cancer biology as well as in the pathogenesis of several neurological disorders such as stroke, spinal cord injury, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). Pharmacological blocking of EphA4 has been suggested to be a therapeutic strategy for these disorders...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28508364/a-novel-2-de-based-proteomic-analysis-to-identify-multiple-substrates-for-specific-protease-in-neuronal-cells
#3
Chiho Kim, Young J Oh
Proteolysis is a process where proteins are broken down into smaller polypeptides or amino acids, comprising one of the important posttranslational modifications of proteins. Since this process is exquisitely achieved by specialized enzymes called proteases under physiological conditions, abnormal protease activity and dysregulation of their substrate proteins are closely associated with a progression of several neurodegenerative diseases including Alzheimer disease, Parkinson disease, stroke, and spinal cord injury...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28505972/alzheimer-s-disease-associated-cerebrospinal-fluid-csf-biomarkers-do-not-correlate-with-csf-volumes-or-csf-production-rate
#4
Mikael Edsbagge, Ulf Andreasson, Khalid Ambarki, Carsten Wikkelsø, Anders Eklund, Kaj Blennow, Henrik Zetterberg, Mats Tullberg
BACKGROUND: Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-β (Aβ42) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of Aβ42, increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively...
May 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28498801/extracellular-truncated-tau-causes-early-presynaptic-dysfunction-associated-with-alzheimer-s-disease-and-other-tauopathies
#5
Fulvio Florenzano, Corsetti Veronica, Gabriele Ciasca, Maria Teresa Ciotti, Anna Pittaluga, Gunedalina Olivero, Marco Feligioni, Filomena Iannuzzi, Valentina Latina, Michele Francesco Maria Sciacca, Alessandro Sinopoli, Danilo Milardi, Giuseppe Pappalardo, Marco De Spirito, Massimiliano Papi, Anna Atlante, Antonella Bobba, Antonella Borreca, Pietro Calissano, Giuseppina Amadoro
The largest part of tau secreted from AD nerve terminals and released in cerebral spinal fluid (CSF) is C-terminally truncated, soluble and unaggregated supporting potential extracellular role(s) of NH2-derived fragments of protein on synaptic dysfunction underlying neurodegenerative tauopathies, including Alzheimer's disease (AD). Here we show that sub-toxic doses of extracellular-applied human NH2tau 26-44 (aka NH2htau) -which is the minimal active moiety of neurotoxic 20-22kDa peptide accumulating in vivo at AD synapses and secreted into parenchyma- acutely provokes presynaptic deficit in K+-evoked glutamate release on hippocampal synaptosomes along with alteration in local Ca2+ dynamics...
April 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28476630/membrane-lipid-therapy-a-historical-perspective-of-membrane-targeted-therapies-from-lipid-bilayer-structure-to-the-pathophysiological-regulation-of-cells
#6
REVIEW
Pablo V Escribá
Our current understanding of membrane lipid composition, structure and functions has led to the investigation of their role in cell signaling, both in healthy and pathological cells. As a consequence, therapies based on the regulation of membrane lipid composition and structure have been recently developed. This novel field, known as Membrane Lipid Therapy, is growing and evolving rapidly, providing treatments that are now in use or that are being studied for their application to oncological disorders, Alzheimer's disease, spinal cord injury, stroke, diabetes, obesity, and neuropathic pain...
May 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28456941/activation-of-glucagon-like-peptide-1-receptor-promotes-neuroprotection-in-experimental-autoimmune-encephalomyelitis-by-reducing-neuroinflammatory-responses
#7
Chi-Ho Lee, Se Jin Jeon, Kyu Suk Cho, Eunjung Moon, Arjun Sapkota, Hee Sook Jun, Jong Hoon Ryu, Ji Woong Choi
The signaling axis of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) has been an important component in overcoming diabetes, and recent reports have uncovered novel beneficial roles of this signaling axis in central nervous system (CNS) disorders, such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia, accelerating processes for exendin-4 repositioning. Here, we studied whether multiple sclerosis (MS) could be a complement to the CNS disorders that are associated with the GLP-1/GLP-1R signaling axis...
April 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28444635/the-leukocentric-theory-of-neurological-disorder-a-manifesto
#8
Robert Fern
Approximately half of the human brain is composed of white matter (WM), a specialized tissue housing the axonal projection of neurons and their necessary supporting glial cells. Axons course long distances from their parent soma, have a delicate structure, large surface area and in many cases are dependent upon a uniquely close morphological arrangement with myelinating oligodendrocyte partners; all factors that may predispose them to injury and disease. WM damage is central to a range of well-characterized disorders including multiple sclerosis and spinal cord injury and is also makes a significant contribution to disorders often considered to be largely focused in gray matter; for example, in stroke where ~49% of injury by volume is located in WM...
April 25, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28442357/dl-3-n-butylphthalide-promotes-neuroplasticity-and-motor-recovery-in-stroke-rats
#9
Yefei Sun, Xi Cheng, Huibin Wang, Xiaopeng Mu, Yifan Liang, YuJia Luo, Huiling Qu, Chuansheng Zhao
BACKGROUNDS AND AIMS: Racemic l-3-n-butylphthalide (dl-NBP), is able to achieve a functional recovery in animal models of cerebral ischemia, vascular dementia, and Alzheimer's disease. In this study, we investigated the effect of dl-NBP on axonal growth, neurogenesis and behavioral performances in rats with cerebral ischemia. METHODS: Focal cerebral ischemia in rats was produced by intracerebral injection of endothelin-1. Starting from postoperative day 7, the experimental rats were administered 70mg/kg dl-NBP by oral gavage for two weeks...
April 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28434268/ubiquitin-c-terminal-hydrolase-l1-uch-l1-as-a-therapeutic-and-diagnostic-target-in-neurodegeneration-neurotrauma-and-neuro-injuries
#10
Kevin K Wang, Zhihui Yang, George Sarkis, Isabel Torres, Vijaya Raghavan
Since its discovery as a major CNS-abundant protein 25 years ago, Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has emerged as an important enzyme in regulating brain protein metabolism, by coupling to the proteasome pathway of protein degradation. Areas covered: UCH-L1 is implicated in both familial and sporadic Parkinson disease and other chronic neurodegenerative diseases. Also, UCH-L1 has been recently emerging as a biofluid-based biomarker for various forms of acute neurotrauma and CNS injury. Expert opinion: The loss of UCH-L1 activity coupled with the gain of proteinopathy function are linked to neurodegeneration such as Parkinsonism and Alzheimer's disease...
April 27, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28431735/characterization-of-an-amyloid-only-transgenic-b6c3-tg-appswe-psen1de9-85dbo-mmjax-mouse-model-of-alzheimer-s-disease
#11
G S Finnie, R Gunnarsson, J Manavis, P C Blumbergs, K A Mander, S Edwards, C Van den Heuvel, J W Finnie
The spatiotemporal pattern of cerebral amyloid deposition, detectable as light microscopically recognizable aggregates in an 'amyloid only' transgenic mouse model of Alzheimer's disease, B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, is reported for the first time in this strain. Monoclonal and polyclonal antibodies were used to detect amyloid deposition immunohistochemically in brains collected from these mice at 3-12 months of age. Amyloid aggregates (20-200 μm) were first found in serial, whole coronal sections of brain at 4 months of age and these increased progressively, plateauing at 11-12 months...
April 18, 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28429640/spinal-alterations-of-reil-insula-in-alzheimer-s-disease
#12
Foivos E Petrides, Ioannis A Mavroudis, Martha Spilioti, Fotios G Chatzinikolaou, Vasiliki G Costa, Stavros J Baloyannis
Alzheimer's disease (AD) is a progressive neurodegenerative disease that involves numerous cellular and biochemical mechanisms resulting in synaptic alterations and extensive neuronal loss. It is primarily characterized by impairment of memory, associated frequently with mood disorders. Continuous studies have shown that insula may be an important target of AD, but neuropathological alterations have not been described extensively. In the present study, we attempted to describe the morphometric and morphological changes of the spines of Reil insula in AD in comparison with normal aging using a silver impregnation technique...
January 1, 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28356028/the-application-of-nanomaterials-in-stem-cell-therapy-for-some-neurological-diseases
#13
Guilong Zhang, Ahsan Ali Khan, Hao Wu, Lukui Chen, Yuchun Gu, Ning Gu
Stem cell therapy provides great promising therapeutic benefits for various neurological disorders. Cell transplantation has emerged as cell replacement application for nerve damage. Recently, nanomaterials obtain wide development in various industrial and medical fields, and nanoparticles have been applied to neuro-medical field for tracking and treating nervous system diseases. Combining stem cell with nanotechnology has raised more and more attentions; and it has demonstrated that it has huge effects on clinical diagnosis and therapeutics in multiple central nervous system diseases, meanwhile, improving prognosis...
March 28, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28314660/alzheimer-s-disease-the-next-frontier-special-report-2017
#14
Jason Karlawish, Clifford R Jack, Walter A Rocca, Heather M Snyder, Maria C Carrillo
In the history of medicine, one means to progress is when we make the decision that our assumptions and definitions of disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. The arc of scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the National Institute on Aging-Alzheimer's Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable measures of biological changes in the brain, commonly known as biological markers, or biomarkers, as part of the diagnosis...
April 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28301040/dimercaprol-is-an-acrolein-scavenger-that-mitigates-acrolein-mediated-pc-12-cells-toxicity-and-reduces-acrolein-in-rat-following-spinal-cord-injury
#15
Ran Tian, Riyi Shi
Acrolein is one of the most toxic byproducts of lipid peroxidation, and it has been shown to be associated with multiple pathological processes in trauma and diseases, including spinal cord injury, multiple sclerosis, and Alzheimer's disease. Therefore, suppressing acrolein using acrolein scavengers has been suggested as a novel strategy of neuroprotection. In an effort to identify effective acrolein scavengers, we have confirmed that dimercaprol, which possesses thiol functional groups, could bind and trap acrolein...
June 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28300657/expression-patterns-of-prune2-is-regulated-by-notch-and-retinoic-acid-signaling-pathways-in-the-zebrafish-embryogenesis
#16
Mrudhula Anuppalle, Sateesh Maddirevula, Ajeet Kumar, Tae-Lin Huh, Joonho Choe, Myungchull Rhee
PRUNE2 has been identified as a susceptible gene for Alzheimer's disease and a marker for leiomyosarcomas. Isoforms of Prune2 regulate neuronal cell differentiation and synaptogenesis. Although expression pattern of Prune2 has been reported in the murine brain, its expression patterns and regulation along vertebrate embryogenesis remain to be further investigated. We thus defined the expression profiles and transcriptional regulation of prune2 in zebrafish embryos. prune2 exhibits maternal expression, but is increased in later embryonic stages, and expressed in the telencephalon, epiphysis cluster, nucleus of the tract of the post optic commissure, spinal cord, cerebellum, tegmentum, anterior lateral line ganglion, posterior lateral line ganglion and rhombomeres 2 through 5...
January 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28284228/interactive-wearable-systems-for-upper-body-rehabilitation-a-systematic-review
#17
REVIEW
Qi Wang, Panos Markopoulos, Bin Yu, Wei Chen, Annick Timmermans
BACKGROUND: The development of interactive rehabilitation technologies which rely on wearable-sensing for upper body rehabilitation is attracting increasing research interest. This paper reviews related research with the aim: 1) To inventory and classify interactive wearable systems for movement and posture monitoring during upper body rehabilitation, regarding the sensing technology, system measurements and feedback conditions; 2) To gauge the wearability of the wearable systems; 3) To inventory the availability of clinical evidence supporting the effectiveness of related technologies...
March 11, 2017: Journal of Neuroengineering and Rehabilitation
https://www.readbyqxmd.com/read/28274814/the-role-of-aquaporin-4-in-synaptic-plasticity-memory-and-disease
#18
REVIEW
Jacqueline A Hubbard, Jenny I Szu, Devin K Binder
Since the discovery of aquaporins, it has become clear that the various mammalian aquaporins play critical physiological roles in water and ion balance in multiple tissues. Aquaporin-4 (AQP4), the principal aquaporin expressed in the central nervous system (CNS, brain and spinal cord), has been shown to mediate CNS water homeostasis. In this review, we summarize new and exciting studies indicating that AQP4 also plays critical and unanticipated roles in synaptic plasticity and memory formation. Next, we consider the role of AQP4 in Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), neuromyelitis optica (NMO), epilepsy, traumatic brain injury (TBI), and stroke...
March 6, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28229085/folate-receptor-alpha-is-more-than-just-a-folate-transporter
#19
Vineet Mohanty, M Rizwan Siddiqui, Tadanori Tomita, Chandra Shekhar Mayanil
Until recently folate receptor alpha (FRα) has only been considered as a folate transporter. However, a novel role of FRα as a transcription factor was reported by our lab. More recently our lab showed a novel pleiotropic role of FRα: (a) direct transcriptional activation of Oct4, Sox2, and Klf4 genes; and (b) repression of biogenesis of miRNAs that target these genes or their effector molecules. These observations beg a question: "Can a simple molecule such as folate be used to manipulate the production and/or differentiation of endogenous neural stem cells (NSCs), which may hold promise for future therapies?" Conditions such as spinal cord injury, motor neuron diseases, Alzheimer's disease and multiple sclerosis may benefit from increasing stem cell pool and promoting specific pathways of differentiation...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28215142/small-molecule-modulation-of-hdac6-activity-the-propitious-therapeutic-strategy-to-vanquish-neurodegenerative-disorders
#20
Shabir Ahmad Ganai
Histone deacetylases (HDACs) are epigenetic enzymes creating the transcriptionally inactive state of chromatin by erasing acetyl moiety from histone and non-histone substrates. HDAC6 modulates several biological pathways in dividing cells as well as in post-mitotic neurons, and has been implicated in the pathophysiology of neurodegeneration. The distinct cellular functions and survival in these cells are reliant on HDAC6-mediated processes including intracellular trafficking, chaperone-mediated stress responses, anti-oxidation and protein degradation...
February 8, 2017: Current Medicinal Chemistry
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