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https://www.readbyqxmd.com/read/28440890/fluorescence-and-autoradiographic-evaluation-of-tau-pet-ligand-pbb3-to-%C3%AE-synuclein-pathology
#1
Shunsuke Koga, Maiko Ono, Naruhiko Sahara, Makoto Higuchi, Dennis W Dickson
BACKGROUND: The tau PET ligand 2-((1E,3E)-4-(6-([(11) C]methylamino)pyridin-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol ([(11) C]PBB3) binds to a wide range of tau pathology; however, binding property of PBB3 to non-tau inclusions remains unknown. To clarify whether [(11) C]PBB3 binds to α-synuclein pathology, reactivity of PBB3 was assessed by in vitro fluorescence and autoradiographic labeling of brain sections from α-synucleinopathies patients. METHOD: Of 10 pure Lewy body disease and 120 multiple system atrophy (MSA) cases in the Mayo Clinic brain bank, we selected 3 Lewy body disease and 4 MSA cases with a range of α-synuclein severity based on the quantitative analysis of α-synuclein burden...
April 25, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28440807/showing-transmitters-the-door-synucleins-accelerate-vesicle-release
#2
Dennis J Selkoe
No abstract text is available yet for this article.
April 25, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28439961/involvement-of-the-cerebellum-in-parkinson-s-disease-and-dementia-with-lewy-bodies
#3
K Seidel, M Bouzrou, N Heidemann, R Krüger, L Schöls, Wfa den Dunnen, H-W Korf, U Rüb
Patient brains with Parkinson's disease or Dementia with Lewy bodies show aggregation of alpha-synuclein in pre-cerebellar brainstem structures. Furthermore, patients exhibit resting tremor, unstable gait and impaired balance which may be associated with cerebellar dysfunction. Therefore, we screened the cerebella of 12 patients with alpha-synucleinopathies for neuropathological changes. Cerebellar nuclei and neighboring white matter displayed numerous aggregates, while lobules were mildly affected. Cerebellar aggregation pathology may suggest a prion-like spread originating from affected precerebellar structures and the high homogeneity between patients with Dementia with Lewy bodies and Parkinson's disease shows that both diseases likely belong to the same neuropathological spectrum...
April 25, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28439627/nigral-injection-of-a-proteasomal-inhibitor-lactacystin-induces-widespread-glial-cell-activation-and-shows-various-phenotypes-of-parkinson-s-disease-in-young-and-adult-mouse
#4
Mari H Savolainen, Katrina Albert, Mikko Airavaara, Timo T Myöhänen
Proteinaceous inclusions, called Lewy bodies, are used as a pathological hallmark for Parkinson's disease (PD). Lewy bodies contain insoluble α-synuclein (aSyn) and many other ubiquitinated proteins, suggesting a role for protein degradation system failure in the PD pathogenesis. Indeed, proteasomal dysfunction has been linked to PD but commonly used in vivo toxin models, such as 6-OHDA or MPTP, do not have a significant effect on the proteasomal system or protein aggregation. Therefore, we wanted to study the characteristics of a proteasomal inhibitor, lactacystin, as a PD model on young and adult mice...
April 24, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28435999/neonatal-propofol-anesthesia-changes-expression-of-synaptic-plasticity-proteins-and-increases-stereotypic-and-anxyolitic-behavior-in-adult-rats
#5
Desanka Milanovic, Vesna Pesic, Natasa Loncarevic-Vasiljkovic, Vladimir Avramovic, Vesna Tesic, Vesna Jevtovic-Todorovic, Selma Kanazir, Sabera Ruzdijic
Propofol is a general anesthetic commonly used in pediatric clinical practices. Experimental findings demonstrate that anesthetics induce widespread apoptosis and cognitive decline in a developing brain. Although anesthesia-mediated neurotoxicity is the most prominent during intense period of synaptogenesis, the effects of an early anesthesia exposure on the synapses are not well understood. The aim of this study was to examine the effects of neonatal propofol anesthesia on the expression of key proteins that participate in synaptogenesis and synaptic plasticity and to evaluate long-term neurobehavioral abnormalities in the mature adult brain...
April 24, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28434973/long-term-oral-kinetin-does-not-protect-against-%C3%AE-synuclein-induced-neurodegeneration-in-rodent-models-of-parkinson-s-disease
#6
Adam L Orr, Florentine U Rutaganira, Daniel de Roulet, Eric J Huang, Nicholas T Hertz, Kevan M Shokat, Ken Nakamura
Mutations in the mitochondrial kinase PTEN-induced putative kinase 1 (PINK1) cause Parkinson's disease (PD), likely by disrupting PINK1's kinase activity. Although the mechanism(s) underlying how this loss of activity causes degeneration remains unclear, increasing PINK1 activity may therapeutically benefit some forms of PD. However, we must first learn whether restoring PINK1 function prevents degeneration in patients harboring PINK1 mutations, or whether boosting PINK1 function can offer protection in more common causes of PD...
April 20, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28434341/acceleration-of-%C3%AE-synuclein-aggregation
#7
Ricardo Gaspar, Georg Meisl, Alexander K Buell, Laurence Young, Clemens F Kaminski, Tuomas P J Knowles, Emma Sparr, Sara Linse
No abstract text is available yet for this article.
March 2017: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/28434243/-clinical-and-neuropathological-characteristics-of-dementia-with-lewy-bodies
#8
János Bencze, Viktória Simon, Erika Bereczki, Réka Majer, Gréta Varkoly, Balázs Murnyák, János Kálmán, Tibor Hortobágyi
Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia. The accurate diagnosis is often possible only by neuropathological examination. The morphologic hallmarks are the presence of α-synuclein-rich Lewy bodies and Lewy neurites, identical to those seen in Parkinson's disease (PD) and Parkinson's disease dementia (PDD). Neurotransmitter deficits, synaptic and ubiquitin-proteasome system (UPS) dysfunction play major role in the pathomechanism. Characteristic symptoms are cognitive fluctuation, parkinsonism and visual hallucinations...
April 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28434076/%C3%AE-synuclein-nonhuman-primate-models-of-parkinson-s-disease
#9
REVIEW
David J Marmion, Jeffrey H Kordower
Proper understanding of the mechanism(s) by which α-synuclein misfolds and propagates may hold the key to unraveling the complex pathophysiology of Parkinson's disease. A more complete understanding of the disease itself, as well as establishing animal models that fully recapitulate pathological and functional disease progression, are needed to develop treatments that will delay, halt or reverse the disease course. Traditional neurotoxin-based animal models fail to mimic crucial aspects of Parkinson's and thus are not relevant for the study of neuroprotection and disease-modifying therapies...
April 22, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28431219/genetic-analysis-of-%C3%AE-synuclein-3-untranslated-region-and-its-corresponding-micrornas-in-relation-to-parkinson-s-compared-to-dementia-with-lewy-bodies
#10
Lidia Tagliafierro, Omolara-Chinue Glenn, Madison E Zamora, Thomas G Beach, Randy L Woltjer, Michael W Lutz, Ornit Chiba-Falek
INTRODUCTION: The α-synuclein (SNCA) gene has been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). METHODS: A computational analysis of SNCA 3' untranslated region to identify potential microRNA (miRNA) binding sites and quantitative real-time PCR to determine their expression in isogenic induced pluripotent stem cell-derived dopaminergic and cholinergic neurons as a model of PD and DLB, respectively, were performed. In addition, we performed a deep sequencing analysis of the SNCA 3' untranslated region of autopsy-confirmed cases of PD, DLB, and normal controls, followed by genetic association analysis of the identified variants...
April 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28430289/evidence-from-spatial-pattern-analysis-for-the-anatomical-spread-of-%C3%AE-synuclein-pathology-in-parkinson-s-disease-dementia
#11
Richard A Armstrong
<i>The objective of this study was to determine whether there is evidence from quantitative morphometry and spatial pattern analysis to support the hypothesis of anatomical spread of -synuclein in Parkinson's disease dementia (PDD). Hence, clustering of -synuclein-immunoreactive Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG) was studied in -synuclein-immunolabeled sections of cortical and limbic regions in 12 cases of PDD. The data suggested that: (1) LB, LN, and LG occurred in clusters which in 63% of regions were regularly distributed parallel to the tissue boundary, (2) in approximately 30% of cortical regions, the estimated cluster size of LB, LN, and LG was within the size range of cellular columns associated with the cortico-cortical pathways, (3) regularly distributed clusters were present in anatomically connected regions, and (4) the clustering pattern was similar to that of prion protein (PrPsc) deposits in Creutzfeldt-Jacob disease (CJD)...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28429355/lewy-pathological-study-on-%C3%AE-synuclein-in-gastrointestinal-tissues-of-prodromal-parkinson-s-disease
#12
Q-B Lu, Z-F Zhu, H-P Zhang, W-F Luo
OBJECTIVE: In the gastrointestinal neural system, the emergence of Lewy Body (LB) is usually earlier than the clinical diagnosis of Parkinson (PD) motor symptoms. Therefore, this study is aimed to explore whether the LB in the gastrointestinal tract of prodromal PD patients. PATIENTS AND METHODS: 98 paraffin embedded tissue specimens from 57 PD patients were collected in the Second Affiliated Hospital of Soochow University archives, as well as 98 tissue specimens of 90 non-PD patients undergone surgical resection...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28429209/analysis-of-gut-microbiota-in-patients-with-parkinson-s-disease
#13
V A Petrov, I V Saltykova, I A Zhukova, V M Alifirova, N G Zhukova, Yu B Dorofeeva, A V Tyakht, B A Kovarsky, D G Alekseev, E S Kostryukova, Yu S Mironova, O P Izhboldina, M A Nikitina, T V Perevozchikova, E A Fait, V V Babenko, M T Vakhitova, V M Govorun, A E Sazonov
Gut microbiota of patients with Parkinson's disease and healthy volunteers was analyzed by the method of high throughput 16S rRNA sequencing of bacterial genomes. In patients with Parkinson's diseases, changes in the content of 9 genera and 15 species of microorganisms were revealed: reduced content of Dorea, Bacteroides, Prevotella, Faecalibacterium, Bacteroides massiliensis, Stoquefichus massiliensis, Bacteroides coprocola, Blautia glucerasea, Dorea longicatena, Bacteroides dorei, Bacteroides plebeus, Prevotella copri, Coprococcus eutactus, and Ruminococcus callidus, and increased content of Christensenella, Catabacter, Lactobacillus, Oscillospira, Bifidobacterium, Christensenella minuta, Catabacter hongkongensis, Lactobacillus mucosae, Ruminococcus bromii, and Papillibacter cinnamivorans...
April 20, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28425704/an-ortho-iminoquinone-compound-reacts-with-lysine-inhibiting-aggregation-while-remodeling-mature-amyloid-fibrils
#14
Luiza Fernandes, Nathália Moraes, Fernanda Savacini Sagrillo, Augusto V Magalhães, Marcela Cristina 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 anti-amyloidogenesis compounds. Herein, we demonstrate that an ortho-iminoquinone (IQ) can be utilized to inhibit amyloid aggregation. Using alpha-synuclein and Aβ1-40 as model systems, we observed that IQ was able to react with lysine residues and reduce amyloid aggregation...
April 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28424751/levodopa-responsive-parkinsonism-in-patients-with-hemochromatosis-case-presentation-and-literature-review
#15
Tarun Girotra, Abhimanyu Mahajan, Christos Sidiropoulos
Hemochromatosis is an autosomal recessive disorder which leads to abnormal iron deposition in the parenchyma of multiple organs causing tissue damage. Accumulation of iron in the brain has been postulated to be associated with several neurodegenerative diseases including Parkinson's disease. The excess iron promotes Parkin and α-synuclein aggregation in the neurons. Excess iron has also been noted in substantia nigra on MRI especially using susceptibility weighted imaging in patients with Parkinson's disease...
2017: Case Reports in Neurological Medicine
https://www.readbyqxmd.com/read/28424577/investigation-of-endocytic-pathways-for-the-internalization-of-exosome-associated-oligomeric-alpha-synuclein
#16
Marion Delenclos, Teodora Trendafilova, Divya Mahesh, Ann M Baine, Simon Moussaud, Irene K Yan, Tushar Patel, Pamela J McLean
Misfolding and aggregation of alpha-synuclein (αsyn) resulting in cytotoxicity is a hallmark of Parkinson's disease (PD) and related synucleinopathies. The recent body of evidence indicates that αsyn can be released from neuronal cells by nonconventional exocytosis involving extracellular vesicles (EVs) such as exosomes. The transfer of αsyn between cells has been proposed to be an important mechanism of disease propagation in PD. To date, exosome trafficking mechanisms, including release and cell-cell transmission, have not been fully described...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28421539/%C3%AE-synuclein-aggregates-with-%C3%AE-amyloid-or-tau-in-human-red-blood-cells-correlation-with-antioxidant-capability-and-physical-exercise-in-human-healthy-subjects
#17
Simona Daniele, Deborah Pietrobono, Jonathan Fusi, Caterina Iofrida, Lucia Chico, Lucia Petrozzi, Annalisa Lo Gerfo, Filippo Baldacci, Fabio Galetta, Gabriele Siciliano, Ubaldo Bonuccelli, Gino Santoro, Maria Letizia Trincavelli, Ferdinando Franzoni, Claudia Martini
Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1-42 (Aβ), and tau, in both brain and peripheral tissue. In addition to homo-oligomers, the role of α-syn interactions with Aβ or tau has gradually emerged. The altered protein accumulation has been related to both oxidative stress and physical activity; nevertheless, no correlation among the presence of peripheral α-syn hetero-aggregates, antioxidant capacity, and physical exercise has been discovered as of yet...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28421431/detection-of-autoantibodies-to-potentially-amyloidogenic-protein-gamma-synuclein-in-the-serum-of-patients-with-amyotrophic-lateral-sclerosis-and-cerebral-circulatory-disorders
#18
A Yu Roman, E A Kovrazhkina, O D Razinskaya, M S Kukharsky, A V Maltsev, R K Ovchinnikov, O A Lytkina, A P Smirnov, A A Moskovtsev, Yu V Borodina, A P Surguchov, A A Ustyugov, N N Ninkina, V I Skvortsova
In this study, we analyzed serum for the presence of antibodies to gamma-synuclein in patients with amyotrophic lateral sclerosis (ALS) compared to the control group of patients with other neurological diseases and healthy control donors. As a result, antibodies against gamma-synuclein are not an ALS-specific feature and have been identified in patients with ALS as well as in the control group patients. Patients with the impaired cerebral circulation showed increased incidence of autoantibodies to gamma-synuclein, yet the difference lacks statistical representativeness due to limited sample size...
January 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28420950/metallothionein-copper-and-alpha-synuclein-in-alpha-synucleinopathies
#19
REVIEW
Yuho Okita, Alexandre N Rcom-H'cheo-Gauthier, Michael Goulding, Roger S Chung, Peter Faller, Dean L Pountney
Metallothioneins (MTs) are proteins that function by metal exchange to regulate the bioavailability of metals, such as zinc and copper. Copper functions in the brain to regulate mitochondria, neurotransmitter production, and cell signaling. Inappropriate copper binding can result in loss of protein function and Cu(I)/(II) redox cycling can generate reactive oxygen species. Copper accumulates in the brain with aging and has been shown to bind alpha-synuclein and initiate its aggregation, the primary aetiological factor in Parkinson's disease (PD), and other alpha-synucleinopathies...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28419968/current-insights-into-pathogenesis-of-parkinson-s-disease-approach-to-mevalonate-pathway-and-protective-role-of-statins
#20
REVIEW
Seyed Soheil Saeedi Saravi, Seyed Sobhan Saeedi Saravi, Katayoun Khoshbin, Ahmad Reza Dehpour
Although Parkinson's disease (PD) is considered as the second most common life threatening age-related neurodegenerative disorder, but the underlying mechanisms for pathogenesis of PD are remained to be fully found. However, a complex relationship between genetic and environmental predisposing factors are involved in progression of PD. Dopaminergic neuronal cell death caused by mutations and accumulation of α-synuclein in Lewy bodies and neurites was suggested as the main strategy for PD, but current studies have paid attention to the role of mevalonate pathway in incidence of neurodegenerative diseases including PD...
April 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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