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Alpha synuclein

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https://www.readbyqxmd.com/read/29790977/alpha-synuclein-aggregates-in-labial-salivary-glands-of-idiopathic-rapid-eye-movement-sleep-behavior-disorder
#1
Alx Iranzo, Sergi Borrego, Isabel Vilaseca, Carles Martí, Mónica Serradell, Raquel Sánchez-Valle, Gabor G Kovacs, Francesc Valldeoriola, Carles Gaig, Joan Santamaria, Eduard Tolosa, Ellen Gelpi
Study Objectives : To assess whether biopsy of the labial minor salivary glands safely detects phosphorylated alpha-synuclein (pAS) deposits in idiopathic REM sleep behavior disorder (IRBD), a condition that precedes the cardinal manifestations of synuclein disorders associated with Lewy type pathology, namely Parkinson disease (PD) and dementia with Lewy bodies (DLB). Methods: In a prospective study, labial biopsy of the minor salivary glands was performed in 62 IRBD patients, 13 PD and 10 DLB patients who were initially diagnosed with IRBD, and in 33 controls...
May 22, 2018: Sleep
https://www.readbyqxmd.com/read/29785351/genetic-inactivation-of-alpha-synuclein-affects-embryonic-development-of-dopaminergic-neurons-of-the-substantia-nigra-but-not-the-ventral-tegmental-area-in-mouse-brain
#2
Tatiana V Tarasova, Olga A Lytkina, Valeria V Goloborshcheva, Larisa N Skuratovskaya, Alexandr I Antohin, Ruslan K Ovchinnikov, Michail S Kukharsky
Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson's disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration...
2018: PeerJ
https://www.readbyqxmd.com/read/29781098/pet-imaging-of-the-influence-of-physiological-and-pathological-%C3%AE-synuclein-on-dopaminergic-and-serotonergic-neurotransmission-in-mouse-models
#3
Elise Levigoureux, Caroline Bouillot, Thierry Baron, Luc Zimmer, Sophie Lancelot
AIMS: Alpha-synuclein (α-syn) aggregation is a neuropathological hallmark of neurodegenerative synucleinopathies. This in vivo study explored glucose metabolism and dopaminergic and serotoninergic neurotransmission in KO α-syn, wild-type mice and an accelerated murine model of synucleinopathy (M83). METHODS: MicroPET acquisitions were performed in all animals aged 5-6 months using five radiotracers exploring brain glucose metabolism ([18 F]FDG), dopamine neurotransmission ([11 C]raclopride, [11 C]PE2I) and serotonin neurotransmission ([18 F]MPPF, [11 C]DASB)...
May 20, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29780350/alpha-synuclein-from-early-synaptic-dysfunction-to-neurodegeneration
#4
REVIEW
Veronica Ghiglieri, Valeria Calabrese, Paolo Calabresi
Over the last two decades, many experimental and clinical studies have provided solid evidence that alpha-synuclein (α-syn), a small, natively unfolded protein, is closely related to Parkinson's disease (PD) pathology. To provide an overview on the different roles of this protein, here we propose a synopsis of seminal and recent studies that explored the many aspects of α-syn. Ranging from the physiological functions to its neurodegenerative potential, the relationship with the possible pathogenesis of PD will be discussed...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29779682/predicting-alpha-synuclein-pathology-by-rem-sleep-behavior-disorder-diagnosis
#5
David R Shprecher, Charles H Adler, Nan Zhang, Joseph G Hentz, Geidy E Serrano, Brittany N Dugger, Holly A Shill, Rodolfo Savica, John N Caviness, Marwan N Sabbagh, Christine M Belden, Erika Driver-Dunckley, Shyamal H Mehta, Lucia I Sue, Kathryn J Davis, Edward Zamrini, Thomas G Beach
Inability to accurately diagnose Lewy type alpha-synucleinopathy (LTS) pre-mortem has been a major obstacle to clinical care and research. Probable REM sleep behavior disorder (PRBD) diagnosed with support of instruments such as the Mayo Sleep Questionnaire (MSQ) may provide a cost effective means of predicting LTS. Since 2007, 602 subjects in the Arizona Study of Aging and Neurodegenerative Disorders had clinician assessment for PRBD (298 with, 304 without support of the MSQ), completed cognitive and movement examinations, and had neuropathological assessment...
May 17, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29769584/publisher-correction-alpha-synuclein-facilitates-to-form-short-unconventional-microtubules-that-have-a-unique-function-in-the-axonal-transport
#6
Shiori Toba, Mingyue Jin, Masami Yamada, Kanako Kumamoto, Sakiko Matsumoto, Takuo Yasunaga, Yuko Fukunaga, Atsuo Miyazawa, Sakiko Fujita, Kyoko Itoh, Shinji Fushiki, Hiroaki Kojima, Hideki Wanibuchi, Yoshiyuki Arai, Takeharu Nagai, Shinji Hirotsune
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29762014/selective-and-sensitive-pull-down-of-amyloid-fibrils-produced-in-vitro-and-in-vivo-by-the-use-of-pentameric-thiophene-coupled-resins
#7
Anna Beatriz Wreden, Luiza Fernandes, Mirian Kelley, Antônio Pereira-Neves, Caroline S Moreira, David R da Rocha, Fernando L Palhano
Protein aggregation is a hallmark of several degenerative diseases, including Alzheimer's disease, Parkinson's disease and familial amyloidosis (Finnish type) (FAF). A method to isolate and detect amyloids is desired for the diagnosis of amyloid diseases. Here, we report the synthesis of pentameric thiophene amyloid ligand (p-FTAA) linked to agarose resin for selective purification of amyloid aggregates produced in vitro and in vivo. Using amyloid fibrils produced in vitro from alpha-synuclein, gelsolin and Aβ1-40 and gelsolin amyloid aggregates extracted from tissue homogenates of a mouse model of FAF, we observed that p-FTAA resin was able to pull down amyloid aggregates...
May 15, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29760287/-multi-organ-distribution-of-alpha-synuclein-pathology-in-dementia-with-lewy-bodies
#8
Koichi Wakabayashi, Yasuo Miki
In Parkinson's disease and dementia with Lewy bodies, neuronal α-synuclein aggregates (Lewy bodies and Lewy neurites) are distributed throughout the nervous system, including the brain, spinal cord, sympathetic ganglia, enteric nervous system, cardiac and pelvic plexuses, submandibular gland, adrenal medulla, and skin. Lewy bodies also occur in 10-20% of neurologically asymptomatic individuals older than 60 years. These cases are called incidental Lewy body disease (ILBD). In ILBD, Lewy bodies can be found in the brain, spinal cord, sympathetic ganglia, visceral autonomic nervous system and skin...
May 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29755323/environmental-enrichment-prevents-transcriptional-disturbances-induced-by-alpha-synuclein-overexpression
#9
Zinah Wassouf, Thomas Hentrich, Sebastian Samer, Carola Rotermund, Philipp J Kahle, Ingrid Ehrlich, Olaf Riess, Nicolas Casadei, Julia M Schulze-Hentrich
Onset and progression of neurodegenerative disorders, including synucleinopathies such as Parkinson's disease, have been associated with various environmental factors. A highly compelling association from a therapeutic point of view has been found between a physically active lifestyle and a significantly reduced risk for Parkinson's disease. Mimicking such conditions in animal models by promoting physical activity, social interactions, and novel surroundings yields in a so-called enriched environment known to enhance adult neurogenesis, increase synaptic plasticity, and decelerate neuronal loss...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29750859/different-structural-conformers-of-monomeric-alpha-synuclein-identified-after-lyophilising-and-freezing
#10
Amberley Stephens, Nadezhda Nespovitaya, Maria Zacharopoulou, Clemens F Kaminski, Jonathan James Phillips, Gabriele S Kaminski Schierle
Understanding the mechanisms behind amyloid protein aggregation in diseases such as Parkinson's and Alzheimer's disease is often hampered by the reproducibility of in vitro assays. Yet, understanding the basic mechanisms of protein misfolding is essential for the development of novel therapeutic strategies. We show here, that for the amyloid protein alpha-synuclein (aSyn), a protein involved in Parkinson's disease (PD), chromatographic buffers and storage conditions can significantly interfere with the overall structure of the protein and thus affect protein aggregation kinetics...
May 11, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29750499/alpha-synuclein-fibrils-contain-multiple-binding-sites-for-small-molecules
#11
Chia-Ju Hsieh, John J Ferrie, Kuiying Xu, Iljung Lee, Thomas J A Graham, Zhude Tu, Jennifer Yu, Dhruva Dhavale, Paul Kotzbauer, E James Petersson, Robert H Mach
The fibrillary aggregation of the protein alpha synuclein (Asyn) is a hallmark of Parkinson's disease, and the identification of small molecule binding sites on fibrils is essential to the development of diagnostic imaging probes. A series of molecular modelling, photoaffinity labeling, mass spectrometry, and radioligand binding studies were conducted on Asyn fibrils. The results of these studies revealed the presence of three different binding sites within fibrillar Asyn capable of binding small molecules with moderate to high affinity...
May 11, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29750243/c9orf72-dipeptide-repeat-poly-ga-inclusions-promote-intracellular-aggregation-of-phosphorylated-tdp-43
#12
Takashi Nonaka, Masami Masuda-Suzukake, Masato Hosokawa, Aki Shimozawa, Shinobu Hirai, Haruo Okado, Masato Hasegawa
Amyotrophic lateral sclerosis and frontotemporal lobar degeneration are neurodegenerative diseases characterized by accumulation of insoluble aggregates of phosphorylated 43-kDa TAR DNA-binding protein (TDP-43), and linked with abnormal expansion of a hexanucleotide repeat in an intron of chromosome 9 open reading frame 72 (C9ORF72). However, the relationship between C9ORF72 mutations and TDP-43 aggregation remains unknown. Non-ATG-dependent translation of C9ORF72 repeats produces dipeptide repeat (DPR) proteins, which form p62-positive aggregates in cerebral cortex and cerebellum of patients...
May 10, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29747899/central-neurocytoma-represents-a-tumor-consisting-of-diverse-neuronal-phenotypes
#13
Branavan Manoranjan, John P Provias
Central neurocytoma (CN) has long been regarded as a neuronal tumor based on the immunohistochemical expression of synaptophysin and the ultrastructural observation of neurosecretory granules, neurites, and synapses. Having diagnosed 11 CNs at our institution over the past thirty years, we set out to conduct an immunohistochemical study to assess the expression profile of neuronal markers across our cases. Markers of interest included synaptophysin, alpha-synuclein, chromogranin, neurofilament, and calretinin...
May 7, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29746402/update-in-therapeutic-strategies-for-parkinson-s-disease
#14
Jaime Kulisevsky, Lais Oliveira, Susan H Fox
PURPOSE OF REVIEW: To review recent advances in therapeutics for motor and nonmotor symptoms of Parkinson's disease. RECENT FINDINGS: Neuroprotection remains a large area of investigation with preliminary safety data on alpha synuclein immunotherapy and glucagon-like peptide-1 agonists. Novel Monoamine Oxidase B and Caetchol-O-methyltransferase-inhibitors for motor fluctuations have shown benefit and are recently approved for clinical use. Long-acting amantadine has also been approved to reduce dyskinesia...
May 8, 2018: Current Opinion in Neurology
https://www.readbyqxmd.com/read/29738845/microrna-7-facilitates-the-degradation-of-alpha-synuclein-and-its-aggregates-by-promoting-autophagy
#15
Doo Chul Choi, Myungsik Yoo, Savan Kabaria, Eunsung Junn
Alpha-Synuclein (α-Syn) is an important protein in the pathogenesis of Parkinson disease (PD) as it accumulates as fibrillar inclusions in affected brain regions including dopaminergic neurons in the substantia nigra. Elevated levels of α-Syn seem to be crucial in mediating its toxicity. Thus, detailed information regarding the regulatory mechanism of α-Syn expression in several layers such as transcription, post-transcription and post-translation is needed in order to devise therapeutic interventions for PD...
May 5, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29734684/comparing-the-folds-of-prions-and-other-pathogenic-amyloids
#16
REVIEW
José Miguel Flores-Fernández, Vineet Rathod, Holger Wille
Pathogenic amyloids are the main feature of several neurodegenerative disorders, such as Creutzfeldt⁻Jakob disease, Alzheimer’s disease, and Parkinson’s disease. High resolution structures of tau paired helical filaments (PHFs), amyloid-β(1-42) (Aβ(1-42)) fibrils, and α-synuclein fibrils were recently reported using cryo-electron microscopy. A high-resolution structure for the infectious prion protein, PrPSc , is not yet available due to its insolubility and its propensity to aggregate, but cryo-electron microscopy, X-ray fiber diffraction, and other approaches have defined the overall architecture of PrPSc as a 4-rung β-solenoid...
May 4, 2018: Pathogens
https://www.readbyqxmd.com/read/29730891/alpha-synuclein-mrna-isoform-formation-and-translation-affected-by-polymorphism-in-the-human-snca-3-utr
#17
Elizabeth S Barrie, Sung-Ha Lee, John T Frater, Maria Kataki, Douglas W Scharre, Wolfgang Sadee
BACKGROUND: Multiple variants in SNCA, encoding alpha-synuclein, a main component of Lewy bodies, are implicated in Parkinson's disease. METHODS: We searched for cis-acting SNCA variants using allelic mRNA ratios in human brain tissues. In a SNCA 3'UTR (2,520 bp) luciferase reporter gene assay, translation in SH-SY5Y cells in the presence of the rs17016074 G/A alleles was measured. To assess clinical impact, we queried neurocognitive genome-wide association studies...
May 6, 2018: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/29725687/the-potential-of-zwitterionic-nanoliposomes-against-neurotoxic-alpha-synuclein-aggregates-in-parkinson-s-disease
#18
Farhang Aliakbari, Hossein Mohammad-Beigi, Nasrollah Rezaei-Ghaleh, Stefan Becker, Faezeh Dehghani Esmatabad, Hadieh Alsadat Eslampanah Seyedi, Hassan Bardania, Amir Tayaranian Marvian, Joanna F Collingwood, Gunna Christiansen, Markus Zweckstetter, Daniel E Otzen, Dina Morshedi
The protein α-synuclein (αSN) aggregates to form fibrils in neuronal cells of Parkinson's patients. Here we report on the effect of neutral (zwitterionic) nanoliposomes (NLPs), supplemented with cholesterol (NLP-Chol) and decorated with PEG (NLP-Chol-PEG), on αSN aggregation and neurotoxicity. Both NLPs retard αSN fibrillization in a concentration-independent fashion. They do so largely by increasing lag time (formation of fibrillization nuclei) rather than elongation (extension of existing nuclei). Interactions between neutral NLPs and αSN may locate to the N-terminus of the protein...
May 4, 2018: Nanoscale
https://www.readbyqxmd.com/read/29725038/-poly-phenol-digested-metabolites-modulate-alpha-synuclein-toxicity-by-regulating-proteostasis
#19
Diana Macedo, Carolina Jardim, Inês Figueira, A Filipa Almeida, Gordon J McDougall, Derek Stewart, Jose E Yuste, Francisco A Tomás-Barberán, Sandra Tenreiro, Tiago F Outeiro, Cláudia N Santos
Parkinson's disease (PD) is an age-related neurodegenerative disease associated with the misfolding and aggregation of alpha-synuclein (aSyn). The molecular underpinnings of PD are still obscure, but nutrition may play an important role in the prevention, onset, and disease progression. Dietary (poly)phenols revert and prevent age-related cognitive decline and neurodegeneration in model systems. However, only limited attempts were made to evaluate the impact of digestion on the bioactivities of (poly)phenols and determine their mechanisms of action...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29716614/lewy-body-like-alpha-synuclein-inclusions-trigger-reactive-microgliosis-prior-to-nigral-degeneration
#20
Megan F Duffy, Timothy J Collier, Joseph R Patterson, Christopher J Kemp, Kelvin C Luk, Malú G Tansey, Katrina L Paumier, Nicholas M Kanaan, Luke D Fischer, Nicole K Polinski, Olivia L Barth, Jacob W Howe, Nishant N Vaikath, Nour K Majbour, Omar M A El-Agnaf, Caryl E Sortwell
BACKGROUND: Converging evidence suggests a role for microglia-mediated neuroinflammation in Parkinson's disease (PD). Animal models of PD can serve as a platform to investigate the role of neuroinflammation in degeneration in PD. However, due to features of the previously available PD models, interpretations of the role of neuroinflammation as a contributor to or a consequence of neurodegeneration have remained elusive. In the present study, we investigated the temporal relationship of neuroinflammation in a model of synucleinopathy following intrastriatal injection of pre-formed alpha-synuclein fibrils (α-syn PFFS)...
May 1, 2018: Journal of Neuroinflammation
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