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https://www.readbyqxmd.com/read/28527958/treadmill-exercise-produces-neuroprotective-effects-in-a-murine-model-of-parkinson-s-disease-by-regulating-the-tlr2-myd88-nf-%C3%AE%C2%BAb-signaling-pathway
#1
Jung-Hoon Koo, Yong-Chul Jang, Dong-Ju Hwang, Hyun-Seob Um, Nam-Hee Lee, Jae-Hoon Jung, Joon-Yong Cho
Parkinson's disease (PD) is characterized by progressive dopamine depletion and a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Treadmill exercise is a promising non-pharmacological approach for reducing the risk of PD and other neuroinflammatory disorders, such as Alzheimer's disease. The goal of this study was to investigate the effects of treadmill exercise on α-synuclein-induced neuroinflammation and neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28520803/multiple-modality-biomarker-prediction-of-cognitive-impairment-in-prospectively-followed-de-novo-parkinson-disease
#2
Chelsea Caspell-Garcia, Tanya Simuni, Duygu Tosun-Turgut, I-Wei Wu, Yu Zhang, Mike Nalls, Andrew Singleton, Leslie A Shaw, Ju-Hee Kang, John Q Trojanowski, Andrew Siderowf, Christopher Coffey, Shirley Lasch, Dag Aarsland, David Burn, Lana M Chahine, Alberto J Espay, Eric D Foster, Keith A Hawkins, Irene Litvan, Irene Richard, Daniel Weintraub
OBJECTIVES: To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments. METHODS: We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition...
2017: PloS One
https://www.readbyqxmd.com/read/28516990/cross-talk-between-neurometals-and-amyloidogenic-proteins-at-the-synapse-and-the-pathogenesis-of-neurodegenerative-diseases
#3
REVIEW
M Kawahara, M Kato-Negishi, K Tanaka
Increasing evidence suggests that disruption of metal homeostasis contributes to the pathogenesis of various neurodegenerative diseases, including Alzheimer's disease, prion diseases, Lewy body diseases, and vascular dementia. Conformational changes of disease-related proteins (amyloidogenic proteins), such as β-amyloid protein, prion proteins, and α-synuclein, are well-established contributors to neurotoxicity and to the pathogenesis of these diseases. Recent studies have demonstrated that these amyloidogenic proteins are metalloproteins that bind trace elements, including zinc, iron, copper, and manganese, and play significant roles in the maintenance of metal homeostasis...
May 18, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28516276/p2x7-receptor-pannexin-1-interaction-mediates-extracellular-alpha-synuclein-induced-atp-release-in-neuroblastoma-sh-sy5y-cells
#4
Anna Wilkaniec, Magdalena Gąssowska, Grzegorz A Czapski, Magdalena Cieślik, Grzegorz Sulkowski, Agata Adamczyk
Abnormalities of alpha-synuclein (ASN), the main component of protein deposits (Lewy bodies), were observed in Parkinson's disease (PD), dementia with Lewy bodies, Alzheimer's disease, and other neurodegenerative disorders. These alterations include increase in the levels of soluble ASN oligomers in the extracellular space. Numerous works have identified several mechanisms of their toxicity, including stimulation of the microglial P2X7 receptor leading to oxidative stress. While the significant role of purinergic signaling-particularly, P2 family receptors-in neurodegenerative disorders is well known, the interaction of extracellular soluble ASN with neuronal purinergic receptors is yet to be studied...
May 17, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28497345/retinol-vitamin-a-increases-%C3%AE-synuclein-%C3%AE-amyloid-peptide-tau-phosphorylation-and-rage-content-in-human-sh-sy5y-neuronal-cell-line
#5
Alice Kunzler, Eduardo Antônio Kolling, Jeferson Delgado da Silva-Jr, Juciano Gasparotto, Matheus Augusto de Bittencourt Pasquali, José Cláudio Fonseca Moreira, Daniel Pens Gelain
Retinoids (vitamin A and derivatives) are recognized as essential factors for central nervous system (CNS) development. Retinol (vitamin A) also was postulated to be a major antioxidant component of diet as it modulates reactive species (RS) production and oxidative stress in biological systems. Oxidative stress plays a major role either in pathogenesis or development of neurodegenerative diseases, or even in both. Here we investigate the role of retinol supplementation to human neuron-derived SH-SY5Y cells over RS production and biochemical markers associated to neurodegenerative diseases expressed at neuronal level in Parkinson's disease and Alzheimer's disease: α-synuclein, β-amyloid peptide, tau phosphorylation and RAGE...
May 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28479587/structure-distribution-and-genetic-profile-of-%C3%AE-synuclein-and-their-potential-clinical-application-in-parkinson-s-disease
#6
Xiaoli Si, Jiali Pu, Baorong Zhang
Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease, is characterized by the loss of nigral dopaminergic neurons. PD leads to a series of clinical symptoms, including motor and non-motor disturbances. α-synuclein, the major component of Lewy bodies, is a hallmark lesion in PD. In this review, we concentrate on presenting the latest research on the structure, distribution, and function of α-synuclein, and its interactions with PD. We also summarize the clinic applications of α-synuclein, which suggest its use as a biomarker, and the latest progress in α-synuclein therapy...
May 2017: Journal of Movement Disorders
https://www.readbyqxmd.com/read/28477284/holocranohistochemistry-enables-the-visualization-of-%C3%AE-synuclein-expression-in-the-murine-olfactory-system-and-discovery-of-its-systemic-anti-microbial-effects
#7
Julianna J Tomlinson, Bojan Shutinoski, Li Dong, Fanyi Meng, Dina Elleithy, Nathalie A Lengacher, Angela P Nguyen, Greg O Cron, Qiubo Jiang, Erik D Roberson, Robert L Nussbaum, Nour K Majbour, Omar M El-Agnaf, Steffany A Bennett, Diane C Lagace, John M Woulfe, Subash Sad, Earl G Brown, Michael G Schlossmacher
Braak and Del Tredici have proposed that typical Parkinson disease (PD) has its origins in the olfactory bulb and gastrointestinal tract. However, the role of the olfactory system has insufficiently been explored in the pathogeneses of PD and Alzheimer disease (AD) in laboratory models. Here, we demonstrate applications of a new method to process mouse heads for microscopy by sectioning, mounting, and staining whole skulls ('holocranohistochemistry'). This technique permits the visualization of the olfactory system from the nasal cavity to mitral cells and dopamine-producing interneurons of glomeruli in the olfactory bulb...
May 5, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28473694/accumulation-of-multiple-neurodegenerative-disease-related-proteins-in-familial-frontotemporal-lobar-degeneration-associated-with-granulin-mutation
#8
Masato Hosokawa, Hiromi Kondo, Geidy E Serrano, Thomas G Beach, Andrew C Robinson, David M Mann, Haruhiko Akiyama, Masato Hasegawa, Tetsuaki Arai
In 2006, mutations in the granulin gene were identified in patients with familial Frontotemporal Lobar Degeneration. Granulin transcript haploinsufficiency has been proposed as a disease mechanism that leads to the loss of functional progranulin protein. Granulin mutations were initially found in tau-negative patients, though recent findings indicate that these mutations are associated with other neurodegenerative disorders with tau pathology, including Alzheimer's disease and corticobasal degeneration. Moreover, a reduction in progranulin in tau transgenic mice is associated with increasing tau accumulation...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28467708/novel-benzothiazole-derivatives-as-fluorescent-probes-for-detection-of-%C3%AE-amyloid-and-%C3%AE-synuclein-aggregates
#9
Hiroyuki Watanabe, Masahiro Ono, Taisuke Ariyoshi, Rikako Katayanagi, Hideo Saji
Deposits of β-amyloid (Aβ) and α-synuclein (α-syn) are the hallmark of Alzheimer's disease (AD) and Parkinson's disease (PD), respectively. The detection of these protein aggregates with fluorescent probes is particularly of interest for preclinical studies using fluorescence microscopy on human brain tissue. In this study, we newly designed and synthesized three push-pull benzothiazole (PP-BTA) derivatives as fluorescent probes for detection of Aβ and α-syn aggregates. Fluorescence intensity of all PP-BTA derivatives significantly increased upon binding to Aβ(1-42) and α-syn aggregates in solution...
May 3, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28460628/investigation-on-the-molecular-interactions-stabilizing-the-structure-of-%C3%AE-synuclein-fibril-an-in-silico-study
#10
Airy Sanjeev, Venkata Satish Kumar Mattaparthi
Amyloid fibrils represent stable form of many misfolded proteins associated with numerous diseases like Parkinson's disease(PD),Type II diabetes and Alzheimer's disease(AD). Lewy Bodies(LB) are the pathological hallmark of PD where long fibrils disrupting the brain's activity that constitutes the main component, α-synuclein. However α-synuclein structure has eluded researchers due to its complexity, insolubility and difficulty of characterizing one protein within a fibril. Recently, a high resolution structure of α-synuclein protein that stacks together forming fibrils in brains of PD patients was identified...
April 27, 2017: Central Nervous System Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28454606/therapeutic-implication-of-autophagy-in-neurodegenerative-diseases
#11
Md Ataur Rahman, Hyewhon Rhim
Autophagy, a catabolic process to maintain intracellular homeostasis, has been recently focus in numerous human disease conditions, such as aging, cancer, development, immunity, longevity, and neurodegeneration. However, sustaining autophagy is essential for cell survival and dysregulate autophagy is anticipated to speed up neurodegeneration progression; although, the actual molecular mechanism is not yet fully understood. In contrast, emerging evidence suggests that basal autophagy is necessary for removal of misfolded aggregation proteins and damaged cellular organelles through lysosomal mediated degradation...
April 29, 2017: BMB Reports
https://www.readbyqxmd.com/read/28453489/changes-of-cerebrospinal-fluid-peptides-due-to-tauopathy
#12
Petra Majerova, Peter Barath, Alena Michalicova, Stanislav Katina, Michal Novak, Andrej Kovac
Alzheimer's disease (AD) and progressive supranuclear palsy are two common neurodegenerative tauopathies, and the most common cause of progressive brain dementia in elderly affecting more than 35 million people. The tauopathies are characterized by abnormal deposition of microtubule associated protein tau into intracellular neurofibrillary tangles composed mainly of the hyperphosphorylated form of the protein. The diagnosis of tauopathies is based on the presence of clinical features and pathological changes...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28453255/characterization-and-identification-of-dityrosine-cross-linked-peptides-using-tandem-mass-spectrometry
#13
Soumya Mukherjee, Eugene A Kapp, Amber Lothian, Anne M Roberts, Yury Vasilev, Berin Boughton, Kevin Jeffrey Barnham, W Mei Kok, Craig A Hutton, Colin L Masters, Ashley Bush, Joseph S Beckman, Somdatta Ghosh Dey, Blaine R Roberts
The use of mass spectrometry coupled with chemical cross-linking of proteins has become a powerful tool for proteins structure and interactions studies. Unlike structural analysis of proteins using chemical reagents specific for lysine or cysteine residues, identification of gas-phase fragmentation patterns of endogenous dityrosine cross-linked peptides have not been investigated. Dityrosine cross-linking in proteins and peptides are clinical markers of oxidative stress, ageing and neurodegenerative diseases including Alzheimer's disease and Parkinson's disease...
April 28, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28425704/an-ortho-iminoquinone-compound-reacts-with-lysine-inhibiting-aggregation-while-remodeling-mature-amyloid-fibrils
#14
Luiza Fernandes, Nathalia Moraes, Fernanda S Sagrillo, Augusto V Magalhães, Marcela C de Moraes, Luciana Romão, Jeffery W Kelly, Debora Foguel, Neil P Grimster, Fernando L Palhano
Protein aggregation is a hallmark of several neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. It has been shown that lysine residues play a key role in the formation of these aggregates. Thus, the ability to disrupt aggregate formation by covalently modifying lysine residues could lead to the discovery of therapeutically relevant antiamyloidogenesis compounds. Herein, we demonstrate that an ortho-iminoquinone (IQ) can be utilized to inhibit amyloid aggregation. Using alpha-synuclein and Aβ1-40 as model amyloidogenic proteins, we observed that IQ was able to react with lysine residues and reduce amyloid aggregation...
May 4, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28410662/lewy-body-disorders
#15
REVIEW
Douglas Galasko
Dementia syndromes associated with Lewy bodies are subdivided into dementia with Lewy bodies (DLB), an underdiagnosed cause of dementia in the elderly, and Parkinson disease with dementia (PDD), cognitive impairment appearing in people diagnosed with Parkinson disease. Their neuropathologic substrates are the widespread distribution of aggregates of the protein α-synuclein in neurons in cortical brain regions, accompanied by variable Alzheimer pathology. Clinical features of DLB and PDD include distinctive changes in cognition, behavior, movement, sleep, and autonomic function...
May 2017: Neurologic Clinics
https://www.readbyqxmd.com/read/28401333/interactions-of-pathological-proteins-in-neurodegenerative-diseases
#16
REVIEW
Tara L Spires-Jones, Johannes Attems, Dietmar Rudolf Thal
Neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal lobar degeneration (FTD), Lewy body disease (LBD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) have in common that protein aggregates represent pathological hallmark lesions. Amyloid β-protein, τ-protein, α-synuclein, and TDP-43 are the most frequently aggregated proteins in these disorders. Although they are assumed to form disease-characteristic aggregates, such as amyloid plaques and neurofibrillary tangles in AD or Lewy bodies in LBD/PD, they are not restricted to these clinical presentations...
April 11, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28395086/regional-overlap-of-pathologies-in-lewy-body-disorders
#17
Martí Colom-Cadena, Oriol Grau-Rivera, Lluís Planellas, Catalina Cerquera, Estrella Morenas, Sergio Helgueta, Laia Muñoz, Jaime Kulisevsky, Maria Jose Martí, Eduard Tolosa, Jordi Clarimon, Alberto Lleó, Ellen Gelpi
Lewy body disorders (LBD) are common neurodegenerative diseases characterized by the presence of aggregated α-synuclein in Lewy bodies and Lewy neurites in the central and peripheral nervous systems. The brains of patients with LBD often display other comorbid pathologies, i.e. insoluble tau, β-amyloid aggregates, TAR DNA-binding protein 43 (TDP-43) deposits, and argyrophilic grain disease (AGD). The incidence and physiological relevance of these concurrent pathological findings remain controversial. We performed a semiquantitative detailed mapping of α-synuclein, tau, β-amyloid (Aβ), TDP-43, and AGD pathologies in 17 areas in 63 LBD cases (44 with Parkinson disease [PD], 28 with dementia, and 19 with dementia with Lewy bodies)...
March 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28390825/changes-in-cd200-and-intercellular-adhesion-molecule-1-icam-1-levels-in-brains-of-lewy-body-disorder-cases-are-associated-with-amounts-of-alzheimer-s-pathology-not-%C3%AE-synuclein-pathology
#18
Douglas G Walker, Lih-Fen Lue, Tiffany M Tang, Charles H Adler, John N Caviness, Marwan N Sabbagh, Geidy E Serrano, Lucia I Sue, Thomas G Beach
Enhanced inflammation has been associated with Alzheimer's disease (AD) and diseases with Lewy body (LB) pathology, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). One issue is whether amyloid and tangle pathology, features of AD, or α-synuclein LB pathology have similar or different effects on brain inflammation. An aim of this study was to examine if certain features of inflammation changed in brains with increasing LB pathology. To assess this, we measured levels of the anti-inflammatory protein CD200 and the pro-inflammatory protein intercellular adhesion molecule-1 (ICAM-1) in cingulate and temporal cortex from a total of 143 cases classified according to the Unified Staging System for LB disorders...
June 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28379416/absence-of-alzheimer-disease-neuropathologic-changes-in-eyes-of-subjects-with-alzheimer-disease
#19
Erik A Williams, Declan McGuone, Matthew P Frosch, Bradley T Hyman, Nora Laver, Anat Stemmer-Rachamimov
Alzheimer disease (AD) is the most common cause of dementia in the elderly, and is characterized by extracellular deposition of β-amyloid and intracellular accumulation of hyperphosphorylated tau protein in the brain. These pathologic findings are identified postmortem. Various visual deficits in AD have been reported and there have been conflicting reports, through imaging and pathology studies, regarding the presence of changes in the globe that mirror Alzheimer changes in the brain. Moreover, both macular degeneration and glaucoma have been variously characterized as having AD-related features...
March 30, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28374864/lack-of-spontaneous-age-related-brain-pathology-in-octodon-degus-a-reappraisal-of-the-model
#20
Mathieu Bourdenx, Sandra Dovero, Marie-Laure Thiolat, Erwan Bezard, Benjamin Dehay
Neurodegenerative diseases are characterized by the degeneration of specific brain areas associated with accumulation of disease-related protein in extra- or intra-cellular deposits. Their preclinical investigations are mostly based on genetically-engineered animals. Despite their interest, these models are often based on high level of disease-related protein expression, thus questioning their relevance to human pathology and calling for the alternate use of ecological models. In the past few years, Octodon degus has emerged as a promising animal model displaying age-dependent Alzheimer's disease-related pathology...
April 4, 2017: Scientific Reports
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