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https://www.readbyqxmd.com/read/29329976/therapeutic-potential-of-spinal-glp-1-receptor-signaling
#1
REVIEW
Dongao Zhang, Gang Lv
GLP-1 signaling pathway has been well studied for its role in regulating glucose homeostasis, as well as its beneficial effects in energy and nutrient metabolism. A number of drugs based on GLP-1 have been used to treat type 2 diabetes mellitus. GLP-1R is expressed in multiple organs and numerous experimental studies have demonstrated that GLP-1 signaling pathway exhibits pro-survival functions in various disorders. In the central nervous system, stimulation of GLP-1R produces neuroprotective effects in specific neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease...
January 9, 2018: Peptides
https://www.readbyqxmd.com/read/29286334/a-single-neonatal-exposure-to-bmaa-in-a-rat-model-produces-neuropathology-consistent-with-neurodegenerative-diseases
#2
Laura Louise Scott, Timothy Grant Downing
Although cyanobacterial β-N-methylamino-l-alanine (BMAA) has been implicated in the development of Alzheimer's Disease (AD), Parkinson's Disease (PD) and Amyotrophic Lateral Sclerosis (ALS), no BMAA animal model has reproduced all the neuropathology typically associated with these neurodegenerative diseases. We present here a neonatal BMAA model that causes β-amyloid deposition, neurofibrillary tangles of hyper-phosphorylated tau, TDP-43 inclusions, Lewy bodies, microbleeds and microgliosis as well as severe neuronal loss in the hippocampus, striatum, substantia nigra pars compacta, and ventral horn of the spinal cord in rats following a single BMAA exposure...
December 29, 2017: Toxins
https://www.readbyqxmd.com/read/29282410/cerebrospinal-fluid-s100b-and-alzheimer-s-disease-biomarkers-in-hip-fracture-patients-with-delirium
#3
Karen Roksund Hov, Nils Bolstad, Ane-Victoria Idland, Henrik Zetterberg, Kaj Blennow, Farrukh A Chaudhry, Frede Frihagen, Johan Ræder, Torgeir Bruun Wyller, Leiv Otto Watne
Objectives: This study aimed to investigate the relationship between cerebrospinal fluid (CSF) S100B astrocyte-derived protein and delirium and to perform stratified analyses according to clinical and CSF markers of dementia. Methods: We performed a prospective cohort study in a university hospital setting. The participants were patients admitted for hip fracture (n = 98) or for elective surgery (n = 50). Delirium was assessed daily perioperatively in hip fracture patients using the Confusion Assessment Method...
September 2017: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/29280981/%C3%AE-n-methylamino-l-alanine-bmaa-toxicity-is-gender-and-exposure-age-dependent-in-rats
#4
Laura Louise Scott, Timothy Grant Downing
Cyanobacterial β-N-methylamino-L-alanine (BMAA) has been suggested as a causative or contributory factor in the development of several neurodegenerative diseases. However, no BMAA animal model has adequately shown clinical or behavioral symptoms that correspond to those seen in either Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS) or Parkinson's Disease (PD). We present here the first data that show that when neonatal rats were exposed to BMAA on postnatal days 3, 4 and 5, but not on gestational day 14 or postnatally on days 7 or 10, several AD and/or PD-related behavioral, locomotor and cognitive deficits developed...
December 27, 2017: Toxins
https://www.readbyqxmd.com/read/29249541/cerebrospinal-fluid-biomarkers-of-alzheimer-s-disease-are-associated-with-carotid-plaque-score-and-hemodynamics-in-intra-and-extra-cranial-arteries-on-ultrasonography
#5
Minoru Kouzuki, Masaya Nagano, Tetsuya Suzuki, Yuto Katsumata, Syouta Nakamura, Ayumi Takamura, Katsuya Urakami
Carotid plaque score (PS) and hemodynamic abnormalities in intra- and extra-cranial arteries are related to Alzheimer's disease (AD) progression. As these parameters are measured conveniently and non-invasively by ultrasonography, we examined their association with cerebral spinal fluid (CSF) AD biomarkers amyloid β (Aβ) and phosphorylated tau (p-tau). Carotid PS, mean flow velocity (MFV) in multiple intra- and extra-cranial arteries, CSF Aβ42 and p-tau, neurocognitive function (assessed by the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale-cognitive subscale, Japanese version), and blood lipids (total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride) were measured in AD patients (n = 42), mild cognitive impairment patients (n = 20), and cognitively normal controls (n = 18)...
December 14, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29240990/wnt-signaling-loss-accelerates-the-appearance-of-neuropathological-hallmarks-of-alzheimer-s-disease-in-j20-app-transgenic-and-wild-type-mice
#6
Cheril Tapia-Rojas, Nibaldo C Inestrosa
Alzheimer's disease (AD) is a neurodegenerative pathology characterized by aggregates of amyloid-β (Aβ) and phosphorylated tau protein, synaptic dysfunction, and spatial memory impairment. The Wnt signaling pathway has several key functions in the adult brain and has been associated with AD, mainly as a neuroprotective factor against Aβ toxicity and tau phosphorylation. However, dysfunction of Wnt/β-catenin signaling might also play a role in the onset and development of the disease. J20 APPswInd transgenic (Tg) mouse model of AD was treated i...
December 14, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29228660/motor-deficits-are-independent-of-axonopathy-in-an-alzheimer-s-disease-mouse-model-of-tgcrnd8-mice
#7
Qiuju Yuan, Jian Yang, Wutian Wu, Zhi-Xiu Lin
There have been an increasing number of reports of non-cognitive symptoms in Alzheimer's disease (AD). Some symptoms are associated with the loss of motor functions, e.g. gait disturbances, disturbed activity level and balance. Consistent with clinical findings, several AD mouse models harboring amyloid pathology develop motor impairment. Although the factors that contribute to the motor deficits have not yet been determined, it has been suggested that axonopathy is one of the key factors that may contribute to this particular feature of the disease...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29185388/%C3%AE-lipoic-acid-functional-fatty-acid-as-a-novel-therapeutic-alternative-for-central-nervous-system-diseases-a-review
#8
Fatemeh Seifar, Mohammad Khalili, Habib Khaledyan, Shirin Amiri Moghadam, Azimeh Izadi, Amirreza Azimi, Seied Kazem Shakouri
OBJECTIVES: α-lipoic acid (ALA) is a natural antioxidant which acts as a cofactor of bioenergetic mitochondrial enzymes. Along with its mitochondrial action, ALA and its reduced form have many biological functions resulting in a wide variety of actions such as anti-inflammation and antioxidant protection, scavenging reactive oxygen species, regenerating other antioxidant agents, such as vitamins C and E, and cytosolic glutathione, chelating the transitional metal ions (e.g. iron and copper), and modulating the signal transduction of nuclear factor...
November 29, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/29176903/axonal-and-myelinic-pathology-in-5xfad-alzheimer-s-mouse-spinal-cord
#9
Tak-Ho Chu, Karen Cummins, Joseph S Sparling, Shigeki Tsutsui, Craig Brideau, K Peter R Nilsson, Jeffrey T Joseph, Peter K Stys
As an extension of the brain, the spinal cord has unique properties which could allow us to gain a better understanding of CNS pathology. The brain and cord share the same cellular components, yet the latter is simpler in cytoarchitecture and connectivity. In Alzheimer's research, virtually all focus is on brain pathology, however it has been shown that transgenic Alzheimer's mouse models accumulate beta amyloid plaques in spinal cord, suggesting that the cord possesses the same molecular machinery and conditions for plaque formation...
2017: PloS One
https://www.readbyqxmd.com/read/29142138/chitotriosidase-chit1-is-increased-in-microglia-and-macrophages-in-spinal-cord-of-amyotrophic-lateral-sclerosis-and-cerebrospinal-fluid-levels-correlate-with-disease-severity-and-progression
#10
Petra Steinacker, Federico Verde, Lubin Fang, Emily Feneberg, Patrick Oeckl, Sigrun Roeber, Sarah Anderl-Straub, Adrian Danek, Janine Diehl-Schmid, Klaus Fassbender, Klaus Fliessbach, Hans Foerstl, Armin Giese, Holger Jahn, Jan Kassubek, Johannes Kornhuber, G Bernhard Landwehrmeyer, Martin Lauer, Elmar Hans Pinkhardt, Johannes Prudlo, Angela Rosenbohm, Anja Schneider, Matthias L Schroeter, Hayrettin Tumani, Christine A F von Arnim, Jochen Weishaupt, Patrick Weydt, Albert C Ludolph, Deniz Yilmazer Hanke, Markus Otto
OBJECTIVES: Neurochemical markers of amyotrophic lateral sclerosis (ALS) that reflect underlying disease mechanisms might help in diagnosis, staging and prediction of outcome. We aimed at determining the origin and differential diagnostic and prognostic potential of the putative marker of microglial activation chitotriosidase (CHIT1). METHODS: Altogether 316 patients were included, comprising patients with sporadic ALS, ALS mimics (disease controls (DCo)), frontotemporal lobar degeneration (FTLD), Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), Parkinson's disease (PD) and healthy controls (Con)...
November 15, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29137141/steroid-and-xenobiotic-receptor-signalling-in-apoptosis-and-autophagy-of-the-nervous-system
#11
REVIEW
Agnieszka Wnuk, Małgorzata Kajta
Apoptosis and autophagy are involved in neural development and in the response of the nervous system to a variety of insults. Apoptosis is responsible for cell elimination, whereas autophagy can eliminate the cells or keep them alive, even in conditions lacking trophic factors. Therefore, both processes may function synergistically or antagonistically. Steroid and xenobiotic receptors are regulators of apoptosis and autophagy; however, their actions in various pathologies are complex. In general, the estrogen (ER), progesterone (PR), and mineralocorticoid (MR) receptors mediate anti-apoptotic signalling, whereas the androgen (AR) and glucocorticoid (GR) receptors participate in pro-apoptotic pathways...
November 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29115051/to-the-end-of-the-line-axonal-mrna-transport-and-local-translation-in-health-and-neurodegenerative-disease
#12
REVIEW
Christopher J Costa, Dianna E Willis
Axons and growth cones, by their very nature far removed from the cell body, encounter unique environments and require distinct populations of proteins. It seems only natural, then, that they have developed mechanisms to locally synthesize a host of proteins required to perform their specialized functions. Acceptance of this ability has taken decades; however, there is now consensus that axons do indeed have the capacity for local translation, and that this capacity is even retained into adulthood. Accumulating evidence supports the role of locally synthesized proteins in the proper development, maintenance, and function of neurons, and newly emerging studies also suggest that disruption in this process has implications in a number of neurodevelopmental and neurodegenerative diseases...
November 7, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/29109789/nucleic-acid-based-theranostics-for-tackling-alzheimer-s-disease
#13
REVIEW
Madhuri Chakravarthy, Suxiang Chen, Peter R Dodd, Rakesh N Veedu
Nucleic acid-based technologies have received significant interest in recent years as novel theranostic strategies for various diseases. The approval by the United States Food and Drug Administration (FDA) of Nusinersen, an antisense oligonucleotide drug, for the treatment of spinal muscular dystrophy highlights the potential of nucleic acids to treat neurological diseases, including Alzheimer's disease (AD). AD is a devastating neurodegenerative disease characterized by progressive impairment of cognitive function and behavior...
2017: Theranostics
https://www.readbyqxmd.com/read/29057990/spinal-cord-injury-and-alzheimer-s-disease-risk-a-population-based-retrospective-cohort-study
#14
Tian-Shin Yeh, Yu-Chun Ho, Cherng-Lan Hsu, Shin-Liang Pan
STUDY DESIGN: Propensity score-matched, retrospective cohort study. OBJECTIVES: To determine the risk of developing Alzheimer's disease (AD) in patients with spinal cord injury (SCI). SETTING: The present study used Taiwan's National Health Insurance Research Database. METHODS: A total of 9257 patients who had ⩾2 ambulatory visits with a diagnosis of SCI in 2001 were included in the SCI group. The non-SCI group consisted of 37,028 propensity score-matched patients without a diagnosis of SCI...
October 23, 2017: Spinal Cord
https://www.readbyqxmd.com/read/29029390/extracellular-truncated-tau-causes-early-presynaptic-dysfunction-associated-with-alzheimer-s-disease-and-other-tauopathies
#15
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, De Spirito Marco, 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 NH2 tau 26-44 (aka NH 2 htau) -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 Ca(2+) dynamics...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29024655/lost-in-transportation-nucleocytoplasmic-transport-defects-in-als-and-other-neurodegenerative-diseases
#16
REVIEW
Hong Joo Kim, J Paul Taylor
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by degeneration of upper and lower motor neurons in the brain and spinal cord. The hallmark pathological feature in most cases of ALS is nuclear depletion and cytoplasmic accumulation of the protein TDP-43 in degenerating neurons. Consistent with this pattern of intracellular protein redistribution, impaired nucleocytoplasmic trafficking has emerged as a mechanism contributing to ALS pathology. Dysfunction in nucleocytoplasmic transport is also an emerging theme in physiological aging and other related neurodegenerative diseases, such as Huntington's and Alzheimer's diseases...
October 11, 2017: Neuron
https://www.readbyqxmd.com/read/28966628/optogenetics-and-its-application-in-neural-degeneration-and-regeneration
#17
REVIEW
Josue D Ordaz, Wei Wu, Xiao-Ming Xu
Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited...
August 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28965171/targeting-of-disordered-proteins-by-small-molecules-in-neurodegenerative-diseases
#18
Francesca Longhena, PierFranco Spano, Arianna Bellucci
The formation of protein aggregates and inclusions in the brain and spinal cord is a common neuropathological feature of a number of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and many others. These are commonly referred as neurodegenerative proteinopathies or protein-misfolding diseases. The main characteristic of protein aggregates in these disorders is the fact that they are enriched in amyloid fibrils. Since protein aggregation is considered to play a central role for the onset of neurodegenerative proteinopathies, research is ongoing to develop strategies aimed at preventing or removing protein aggregation in the brain of affected patients...
October 1, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28963550/proteomic-mapping-of-differentially-vulnerable-pre-synaptic-populations-identifies-regulators-of-neuronal-stability-in-vivo
#19
Maica Llavero Hurtado, Heidi R Fuller, Andrew M S Wong, Samantha L Eaton, Thomas H Gillingwater, Giuseppa Pennetta, Jonathan D Cooper, Thomas M Wishart
Synapses are an early pathological target in many neurodegenerative diseases ranging from well-known adult onset conditions such as Alzheimer and Parkinson disease to neurodegenerative conditions of childhood such as spinal muscular atrophy (SMA) and neuronal ceroid lipofuscinosis (NCLs). However, the reasons why synapses are particularly vulnerable to such a broad range of neurodegeneration inducing stimuli remains unknown. To identify molecular modulators of synaptic stability and degeneration, we have used the Cln3 (-/-) mouse model of a juvenile form of NCL...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28940129/the-role-of-smurf1-in-neuronal-necroptosis-after-lipopolysaccharide-induced-neuroinflammation
#20
Lifei Shao, Xiaojuan Liu, Shunxing Zhu, Chun Liu, Yilu Gao, Xide Xu
The role of inflammation in neurological disorders such as Alzheimer's disease and Parkinson's disease is gradually recognized and leads to an urgent challenge. Smad ubiquitination regulatory factor 1 (Smurf1), one member of the HECT family, is up-regulated by proinflammatory cytokines and associated with apoptosis in acute spinal cord injury. However, the function of Smurf1 through promoting neuronal necroptosis is still limited in the central nervous system (CNS). Hence, we developed a neuroinflammatory model in adult rats following lipopolysaccharide (LPS) lateral ventral injection to elaborate whether Smurf1 is involved in necroptosis in CNS injury...
September 22, 2017: Cellular and Molecular Neurobiology
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