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https://www.readbyqxmd.com/read/29130469/-heparan-sulphates-amyloidosis-and-neurodegeneration
#1
REVIEW
C Vera, J A Alvarez-Orozco, A Maiza, S Chantepie, R N Chehin, M O Ouidja, D Papy-Garcia
INTRODUCTION: A number of neurodegenerative disorders have been linked directly to the accumulation of amyloid fibres. These fibres are made up of proteins or peptides with altered structures and which join together in vivo in association with heparan sulphate-type polysaccharides. AIMS: To examine the most recent concepts in the biology of heparan sulphates and their role in the aggregation of the peptide Abeta, of tau protein, of alpha-synuclein and of prions...
November 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/29115515/serum-microrna-expression-profiling-in-patients-with-multiple-system-atrophy
#2
Kodai Kume, Hisakazu Iwama, Kazushi Deguchi, Kazuyo Ikeda, Tadayuki Takata, Yohei Kokudo, Masaki Kamada, Keiko Fujikawa, Kayo Hirose, Hisashi Masugata, Tetsuo Touge, Tsutomu Masaki
Multiple system atrophy (MSA) is a sporadic neurodegenerative disease that is pathologically characterized by α‑synuclein positive glial cytoplasmic inclusions in oligodendrocytes. The clinical diagnosis of MSA is often challenging as there are no established biomarkers and diagnoses are now based on clinical findings alone. At present, the etiology and pathogenesis of MSA are unclear. It has been reported that dysregulation of microRNA (miRNA/miR) serves an important role in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis...
November 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115353/lysophosphatidylcholine-modulates-the-aggregation-of-human-islet-amyloid-polypeptide
#3
Yanting Xing, Emily H Pilkington, Miaoyi Wang, Cameron J Nowell, Aleksandr Kakinen, Yunxiang Sun, Bo Wang, Thomas P Davis, Feng Ding, Pu Chun Ke
Amyloid aggregation of human islet amyloid polypeptide (IAPP) is a hallmark of type 2 diabetes (T2D), a metabolic disease and a global epidemic. Although IAPP is synthesized in pancreatic β-cells, its fibrils and plaques are found in the extracellular space indicating a causative transmembrane process. Numerous biophysical studies have revealed that cell membranes as well as model lipid vesicles promote the aggregation of amyloid-β (associated with Alzheimer's), α-synuclein (associated with Parkinson's) and IAPP, through electrostatic and hydrophobic interactions between the proteins/peptides and lipid membranes...
November 8, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29114657/chemistry-of-mammalian-metallothioneins-and-their-interaction-with-amyloidogenic-peptides-and-proteins
#4
Elena Atrián-Blasco, Alice Santoro, Dean L Pountney, Gabriele Meloni, Christelle Hureau, Peter Faller
Cu and Zn ions are essential in most living beings. Their metabolism is critical for health and mis-metabolism can be lethal. In the last two decades, a large body of evidence has reported the role of copper, zinc and iron, and oxidative stress in several neurodegenerative diseases like Alzheimer's, Parkinson's, prion diseases, etc. To what extent this mis-metabolism is causative or a consequence of these diseases is still a matter of research. In this context metallothioneins (MTs) appear to play a central gate-keeper role in controlling aberrant metal-protein interactions...
November 8, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/29111606/incubation-with-cu-ii-and-zn-ii-salts-enhances-maldi-tof-mass-spectra-of-amyloid-beta-and-%C3%AE-synuclein-toward-in-vivo-analysis
#5
Andrea R Kelley, Madeline E Colley, George Perry, Stephan B H Bach
Insoluble senile plaque aggregates are indicative of Alzheimer's disease (AD) pathology. A similar phenomenon occurs in Parkinson's disease (PD) with the build-up of Lewy bodies. The analysis of senile plaques, and other brain samples, from AD and PD patients by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has advantages but also presents obstacles due to the nature of the processes utilized in isolation procedures and storage. Salts, buffers, and detergents necessary in isolation of biological species may cause adducts and ion suppression that convolute the spectra obtained...
November 7, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/29111028/csf-biomarkers-%C3%AE-amyloid-tau-proteins-and-a-synuclein-in-the-differential-diagnosis-of-parkinson-plus-syndromes
#6
Vasilios C Constantinides, George P Paraskevas, Evangelia Emmanouilidou, Olga Petropoulou, Anastasia Bougea, Kostas Vekrellis, Ioannis Evdokimidis, Eleftherios Stamboulis, Elisabeth Kapaki
INTRODUCTION: Differential diagnosis of Parkinson-plus patients (PSP, CBD, MSA) and Parkinson's disease (PD) patients is often not straightforward, particularly in atypical cases or at the initial stages of the diseases. Classic CSF biomarkers (amyloid-beta - Aβ42, tau protein - τT and phosphorylated tau protein - τP-181) are established biomarkers in the diagnosis of Alzheimer's disease (AD). CSF a-synuclein (α-syn) has emerged as a promising biomarker in patients with Parkinsonism...
November 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29104136/nucleic-acid-aptamers-for-neurodegenerative-diseases
#7
REVIEW
Alix Bouvier-Müller, Frédéric Ducongé
The increased incidence of neurodegenerative diseases represents a huge challenge for societies. These diseases are characterized by neuronal death and include several different pathologies, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease and transmissible spongiform encephalopathies. Most of these pathologies are often associated with the aggregation of misfolded proteins, such as amyloid-ß, tau, α-synuclein, huntingtin and prion proteins. However, the precise mechanisms that lead to neuronal dysfunction and death in these diseases remain poorly understood...
November 2, 2017: Biochimie
https://www.readbyqxmd.com/read/29096697/race-modifies-the-relationship-between-cognition-and-alzheimer-s-disease-cerebrospinal-fluid-biomarkers
#8
Jennifer C Howell, Kelly D Watts, Monica W Parker, Junjie Wu, Alexander Kollhoff, Thomas S Wingo, Cornelya D Dorbin, Deqiang Qiu, William T Hu
BACKGROUND: African Americans have been reported to have a higher prevalence of Alzheimer's disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD...
November 2, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28992347/common-molecular-pathogenesis-of-disease-related-intrinsically-disordered-proteins-revealed-by-nmr-analysis
#9
Yoshiki Shigemitsu, Hidekazu Hiroaki
Intrinsically disordered proteins (IDPs) are either completely unstructured or contain large disordered regions in their native state; they have drawn much attention in the field of molecular pathology. Some of them substantially tend to form protein self-assemblies, such as toxic or non-toxic aggregates and fibrils, and have been postulated to relate to diseases. These disease-related IDPs include Aβ(1-42) [Alzheimer's disease (AD)], Tau (AD and tauopathy), α-synuclein (Parkinson's disease), and p53 (cancer)...
September 11, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28987195/comorbidities
#10
Irina Alafuzoff, Gabor G Kovacs
The term comorbidities or mixed pathologies is used when brain tissue, a surgical sample, or postmortem brain displays a mixture of protein alterations or other pathologies. Most of the alterations when seen in sufficient extent are considered causative, are related to a certain clinical phenotype, i.e., when hyperphosphorylated τ (HPτ) is observed in occipital cortex concomitant with β-amyloid (Aβ), the diagnosis is Alzheimer disease (AD). When HPτ is observed in hippocampal structures in a subject with extensive and widespread α-synuclein pathology, a Lewy body disease (LBD), the HPτ pathology is considered as a concomitant alteration...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28966932/frequency-of-gba-variants-in-autopsy-proven-multiple-system-atrophy
#11
Miriam Sklerov, Un Jung Kang, Christopher Liong, Lorraine Clark, Karen Marder, Michael Pauciulo, William C Nichols, Wendy K Chung, Lawrence S Honig, Etty Cortes, Jean Paul Vonsattel, Roy N Alcalay
BACKGROUND: Multiple system atrophy (MSA) is marked by abnormal inclusions of alpha-synuclein in oligodendrogliocytes. Etiology remains unknown. Variants in the glucocerebrosidase gene have been associated with other synucleinopathies, dementia with Lewy bodies and Parkinson disease. It is unclear whether glucocerebrosidase variants are associated with MSA. OBJECTIVES: To analyze the frequency of glucocerebrosidase gene variants among autopsy-proven cases of MSA at a brain bank in New York City...
July 2017: Movement Disorders Clinical Practice
https://www.readbyqxmd.com/read/28964772/prion-like-transmission-of-%C3%AE-synuclein-pathology-in-the-context-of-an-nfl-null-background
#12
Nicola J Rutherford, Mieu Brooks, Cara J Riffe, Kimberly-Marie M Gorion, Jasie K Howard, Jess-Karan S Dhillon, Benoit I Giasson
Neurofilaments are a major component of the axonal cytoskeleton in neurons and have been implicated in a number of neurodegenerative diseases due to their presence within characteristic pathological inclusions. Their contributions to these diseases are not yet fully understood, but previous studies investigated the effects of ablating the obligate subunit of neurofilaments, low molecular mass neurofilament subunit (NFL), on disease phenotypes in transgenic mouse models of Alzheimer's disease and tauopathy. Here, we tested the effects of ablating NFL in α-synuclein M83 transgenic mice expressing the human pathogenic A53T mutation, by breeding them onto an NFL null background...
November 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28960544/possible-concurrence-of-tdp-43-tau-and-other-proteins-in-amyotrophic-lateral-sclerosis-frontotemporal-lobar-degeneration
#13
REVIEW
Takahiro Takeda
Transactivation response DNA-binding protein 43 kDa (TDP-43) has been regarded as a major component of ubiquitin-positive/tau-negative inclusions of motor neurons and the frontotemporal cortices in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Neurofibrillary tangles (NFT), an example of tau-positive inclusions, are biochemically and morphologically distinguished from TDP-43-positive inclusions, and are one of the pathological core features of Alzheimer disease (AD). Although ALS/FTLD and AD are distinct clinical entities, they can coexist in an individual patient...
September 27, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28933595/phosphoproteome-based-kinase-activity-profiling-reveals-the-critical-role-of-map2k2-and-plk1-in-neuronal-autophagy
#14
Lei-Lei Chen, Yong-Bo Wang, Ju-Xian Song, Wan-Kun Deng, Jia-Hong Lu, Li-Li Ma, Chuan-Bin Yang, Min Li, Yu Xue
Recent studies have demonstrated that dysregulation of macroautophagy/autophagy may play a central role in the pathogenesis of neurodegenerative disorders, and the induction of autophagy protects against the toxic insults of aggregate-prone proteins by enhancing their clearance. Thus, autophagy has become a promising therapeutic target against neurodegenerative diseases. In this study, quantitative phosphoproteomic profiling together with a computational analysis was performed to delineate the phosphorylation signaling networks regulated by 2 natural neuroprotective autophagy enhancers, corynoxine (Cory) and corynoxine B (Cory B)...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28922400/protein-folding-misfolding-and-aggregation-the-importance-of-two-electron-stabilizing-interactions
#15
Andrzej Stanisław Cieplak
Proteins associated with neurodegenerative diseases are highly pleiomorphic and may adopt an all-α-helical fold in one environment, assemble into all-β-sheet or collapse into a coil in another, and rapidly polymerize in yet another one via divergent aggregation pathways that yield broad diversity of aggregates' morphology. A thorough understanding of this behaviour may be necessary to develop a treatment for Alzheimer's and related disorders. Unfortunately, our present comprehension of folding and misfolding is limited for want of a physicochemical theory of protein secondary and tertiary structure...
2017: PloS One
https://www.readbyqxmd.com/read/28903492/editor-s-highlight-nlrp3-is-required-for-inflammatory-changes-and-nigral-cell-loss-resulting-from-chronic-intragastric-rotenone-exposure-in-mice
#16
Eileen M Martinez, Alison L Young, Yash R Patankar, Brent L Berwin, Li Wang, Katharine M von Herrmann, Jaclyn M Weier, Matthew C Havrda
Complex interactions between genetic and environmental factors are widely believed to underlie the incidence and progression of Parkinson's disease (PD). Rotenone is a naturally occurring metabolic toxin employed as an insecticide and piscicide identified as a risk factor for the development of PD in agricultural workers. The Nlrp3 inflammasome is an intracellular mediator that can initiate an inflammatory cascade in response to cellular stress. Reports by others indicating that NLRP3 expression was detectable in tissues obtained from Alzheimer's disease patients and that the PD-associated protein α-synuclein could activate inflammasomes in cultured glial cells, prompted us to test the prediction that Nlrp3 was required for the development of Parkinson's-like changes resulting from rotenone exposure in mice...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28882310/studying-tau-protein-propagation-and-pathology-in-the-mouse-brain-using-adeno-associated-viruses
#17
Susanne Wegmann, Rachel E Bennett, Ana S Amaral, Bradley T Hyman
The progressive spread of pathological brain lesions containing aggregated tau protein is a hallmark of Alzheimer's disease and other neurodegenerative diseases. In AD, this process follows a distinct pattern along neuronal connections from the entorhinal cortex to hippocampal areas and further on through the limbic system. In other tauopathies, the spread of tau appears less hierarchical throughout the brain, and also nonpathological tau is reported to cross-synaptic connections in the brain. To be able to study the process of cell-to-cell transport of tau and the associated neurotoxicity in the brain in vivo, adeno-associated virus-mediated expression of tau can be used to express different forms of tau in distinct brain areas in rodent models...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28877262/the-er-retention-protein-rer1-promotes-alpha-synuclein-degradation-via-the-proteasome
#18
Hyo-Jin Park, Daniel Ryu, Mayur Parmar, Benoit I Giasson, Nikolaus R McFarland
Abnormal accumulation of α-synuclein (αSyn) has been linked to endoplasmic-reticulum (ER) stress, defective intracellular protein/vesicle trafficking, and cytotoxicity. Targeting factors involved in ER-related protein processing and trafficking may, therefore, be a key to modulating αSyn levels and associated toxicity. Recently retention in endoplasmic reticulum 1 (RER1) has been identified as an important ER retrieval/retention factor for Alzheimer's disease proteins and negatively regulates amyloid-β peptide levels...
2017: PloS One
https://www.readbyqxmd.com/read/28869766/vaccination-strategies-in-tauopathies-and-synucleinopathies
#19
REVIEW
Anne K Braczynski, Jörg B Schulz, Jan-Philipp Bach
Vaccination therapies constitute potential treatment options in neurodegenerative disorders such as Alzheimer disease or Parkinson disease. While a lot of research has been performed on vaccination against extracellular amyloid β, the focus recently shifted toward vaccination against the intracellular proteins tau and α-synuclein, with promising results in terms of protein accumulation reduction. In this review, we briefly summarize lessons to be learned from clinical vaccination trials in Alzheimer disease that target amyloid β...
September 4, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28863860/discoidin-domain-receptor-inhibition-reduces-neuropathology-and-attenuates-inflammation-in-neurodegeneration-models
#20
Michaeline Hebron, Margo Peyton, Xiaoguang Liu, Xiaokong Gao, Ruochong Wang, Irina Lonskaya, Charbel E-H Moussa
The role of cell surface tyrosine kinase collagen-activated receptors known as discoidin domain receptors (DDRs) is unknown in neurodegenerative diseases. We detect up-regulation in DDRs level in post-mortem Alzheimer and Parkinson brains. Lentiviral shRNA knockdown of DDR1 and DDR2 reduces the levels of α-synuclein, tau, and β-amyloid and prevents cell loss in vivo and in vitro. DDR1 and DDR2 knockdown alters brain immunity and significantly reduces the level of triggering receptor expressed on myeloid cells (TREM)-2 and microglia...
October 15, 2017: Journal of Neuroimmunology
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