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synucleinopathy

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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/29784534/presynaptic-dopaminergic-neuroimaging-in-rem-sleep-behavior-disorder-a-systematic-review-and-meta-analysis
#2
REVIEW
Matteo Bauckneht, Andrea Chincarini, Fabrizio De Carli, Michele Terzaghi, Silvia Morbelli, Flavio Nobili, Dario Arnaldi
The presence of polysomnography-confirmed REM sleep behavior disorder (RBD) is the stronger risk factor for having prodromal Parkinson disease (PD), followed by abnormal presynaptic dopaminergic radionuclide neuroimaging. Aim of the review is to conduct a meta-analysis of literature data regarding presynaptic dopaminergic neuroimaging in RBD. A literature search was conducted, resulting in 16 papers that met the inclusion criteria. Clinical and neuroimaging data were extracted. The studies are heterogeneous, especially for neuroimaging methodology...
April 22, 2018: Sleep Medicine Reviews
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/29780321/toll-like-receptor-2-signaling-and-current-approaches-for-therapeutic-modulation-in-synucleinopathies
#4
REVIEW
Ian F Caplan, Kathleen A Maguire-Zeiss
The innate immune response in the central nervous system (CNS) is implicated as both beneficial and detrimental to health. Integral to this process are microglia, the resident immune cells of the CNS. Microglia express a wide variety of pattern-recognition receptors, such as Toll-like receptors, that detect changes in the neural environment. The activation of microglia and the subsequent proinflammatory response has become increasingly relevant to synucleinopathies, including Parkinson's disease the second most prevalent neurodegenerative disease...
2018: Frontiers in Pharmacology
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/29776378/differential-induction-of-mutant-sod1-misfolding-and-aggregation-by-tau-and-%C3%AE-synuclein-pathology
#6
Michael C Pace, Guilian Xu, Susan Fromholt, John Howard, Benoit I Giasson, Jada Lewis, David R Borchelt
BACKGROUND: Prior studies in C. elegans demonstrated that the expression of aggregation-prone polyglutamine proteins in muscle wall cells compromised the folding of co-expressed temperature-sensitive proteins, prompting interest in whether the accumulation of a misfolded protein in pathologic features of human neurodegenerative disease burdens cellular proteostatic machinery in a manner that impairs the folding of other cellular proteins. METHODS: Mice expressing high levels of mutant forms of tau and α-synuclein (αSyn), which develop inclusion pathologies of the mutant protein in brain and spinal cord, were crossed to mice expressing low levels of mutant superoxide dismutase 1 fused to yellow fluorescent protein (G85R-SOD1:YFP) for aging and neuropathological evaluation...
May 18, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29770111/chronic-caffeine-treatment-protects-against-%C3%AE-synucleinopathy-by-reestablishing-autophagy-activity-in-the-mouse-striatum
#7
Yanan Luan, Xiangpeng Ren, Wu Zheng, Zhenhai Zeng, Yingzi Guo, Zhidong Hou, Wei Guo, Xingjun Chen, Fei Li, Jiang-Fan Chen
Despite converging epidemiological evidence for the inverse relationship of regular caffeine consumption and risk of developing Parkinson's disease (PD) with animal studies demonstrating protective effect of caffeine in various neurotoxin models of PD, whether caffeine can protect against mutant α-synuclein (α-Syn) A53T-induced neurotoxicity in intact animals has not been examined. Here, we determined the effect of chronic caffeine treatment using the α-Syn fibril model of PD by intra-striatal injection of preformed A53T α-Syn fibrils...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29765223/efficacy-of-denosumab-in-two-cases-with-multiple-system-atrophy-and-osteoporosis
#8
Masashi Uehara, Yukio Nakamura, Jun Takahashi, Takako Suzuki, Hiroyuki Kato
Background: Multiple-system atrophy (MSA) is an α-synucleinopathy with a very aggressive course and poor prognosis, which lacks efficient treatment. Thus, MSA represents a serious health and social problem. Progressive stridor and acute laryngeal obstruction likely occur in MSA; however, little is known about the bone metabolism or efficacy of bone absorption drugs, such as denosumab, in osteoporosis with MSA. Case presentation and methods: Two male patients with osteoporosis in MSA presented to our institution (at 54 and 68 years of age)...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29762036/biochemical-profiling-of-the-brain-and-blood-metabolome-in-a-mouse-model-of-prodromal-parkinson-s-disease-reveal-distinct-metabolic-profiles
#9
Stewart F Graham, Nowlen L Rey, Ali Yilmaz, Praveen Kumar, Zachary Madaj, Michael Maddens, Ray O Bahado-Singh, Katelyn Becker, Emily Schulz, Lindsay K Meyerdirk, Jennifer A Steiner, Jiyan Ma, Patrik Brundin
Parkinson's disease is the second most common neurodegenerative disease. In the vast majority of cases the origin is not genetic and the cause is not well understood, although progressive accumulation of α-synuclein aggregates appears central to the pathogenesis. Currently, treatments that slow disease progression are lacking and there are no robust biomarkers that can facilitate development of such treatments, or act as aids in early diagnosis. Therefore, we have defined metabolomic changes in the brain and serum in an animal model of prodromal Parkinson's disease...
May 15, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29760292/-targeting-transcellular-transport-of-%C3%AE-synuclein-for-developing-disease-modifying-therapies-for-synucleinopathy
#10
Takafumi Hasegawa
Parkinson's disease (PD) is the second most common neurodegenerative disorder and it is characterized by progressive physical disability along with a variety of non-motor symptoms. Drugs that replenish dopamine can partly alleviate the motor symptoms; however, they do not cure the disease itself. Therefore, there is an urgent need for disease modifying therapies that would delay or prevent neurodegeneration. Increasing evidence suggests that α-synuclein, a key molecule in PD, is secreted into the extracellular environment and can be transported from cell-to-cell, thereby affecting the physiological state of the neighboring cells in a prion-like manner...
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
#11
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/29752409/specific-glycosaminoglycan-chain-length-and-sulfation-patterns-are-required-for-cell-uptake-of-tau-vs-%C3%AE-synuclein-and-%C3%AE-amyloid-aggregates
#12
Barbara E Stopschinski, Brandon B Holmes, Gregory M Miller, Victor A Manon, Jaime Vaquer-Alicea, William L Prueitt, Linda C Hsieh-Wilson, Marc I Diamond
Transcellular propagation of protein aggregate "seeds" has been proposed to mediate the progression of neurodegenerative diseases in tauopathies and α-synucleinopathies. We previously reported that tau and α-synuclein aggregates bind heparan sulfate proteoglycans (HSPGs) on the cell surface, promoting cellular uptake and intracellular seeding. However, the specificity and binding mode of these protein aggregates to HSPGs remain unknown. Here, we measured direct binding to modified heparins to determine the size and sulfation requirements for tau, α-synuclein, and β-amyloid (Aβ) aggregate binding to glycosaminoglycans (GAGs)...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29747690/a53t-%C3%AE-synuclein-overexpression-in-murine-locus-coeruleus-induces-parkinson-s-disease-like-pathology-in-neurons-and-glia
#13
Martin Timo Henrich, Fanni Fruzsina Geibl, Bolam Lee, Wei-Hua Chiu, James Benjamin Koprich, Jonathan Michael Brotchie, Lars Timmermann, Niels Decher, Lina Anita Matschke, Wolfgang Hermann Oertel
Degeneration of noradrenergic locus coeruleus neurons occurs during the prodromal phase of Parkinson's disease and contributes to a variety of non-motor symptoms, e.g. depression, anxiety and REM sleep behavior disorder. This study was designed to establish the first locus coeruleus α-synucleinopathy mouse model, which should provide sufficient information about the time-course of noradrenergic neurodegeneration, replicate cardinal histopathological features of the human Parkinson's disease neuropathology and finally lead to robust histological markers, which are sufficient to assess the pathological changes in a quantitative and qualitative way...
May 10, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29743672/cellular-milieu-imparts-distinct-pathological-%C3%AE-synuclein-strains-in-%C3%AE-synucleinopathies
#14
Chao Peng, Ronald J Gathagan, Dustin J Covell, Coraima Medellin, Anna Stieber, John L Robinson, Bin Zhang, Rose M Pitkin, Modupe F Olufemi, Kelvin C Luk, John Q Trojanowski, Virginia M-Y Lee
In Lewy body diseases-including Parkinson's disease, without or with dementia, dementia with Lewy bodies, and Alzheimer's disease with Lewy body co-pathology 1 -α-synuclein (α-Syn) aggregates in neurons as Lewy bodies and Lewy neurites 2 . By contrast, in multiple system atrophy α-Syn accumulates mainly in oligodendrocytes as glial cytoplasmic inclusions (GCIs) 3 . Here we report that pathological α-Syn in GCIs and Lewy bodies (GCI-α-Syn and LB-α-Syn, respectively) is conformationally and biologically distinct...
May 9, 2018: Nature
https://www.readbyqxmd.com/read/29738880/the-interaction-of-%C3%AE-synuclein-and-tau-a-molecular-conspiracy-in-neurodegeneration
#15
REVIEW
Xu Yan, Riikka-Liisa Uronen, Henri J Huttunen
α-synuclein and Tau are proteins prone to pathological misfolding and aggregation that are normally found in the presynaptic and axonal compartments of neurons. Misfolding initiates a homo-oligomerization and aggregation cascade culminating in cerebral accumulation of aggregated α-synuclein and Tau in insoluble protein inclusions in multiple neurodegenerative diseases. Traditionally, α-synuclein-containing Lewy bodies have been associated with Parkinson's disease and Tau-containing neurofibrillary tangles with Alzheimer's disease and various frontotemporal dementia syndromes...
May 5, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29738845/microrna-7-facilitates-the-degradation-of-alpha-synuclein-and-its-aggregates-by-promoting-autophagy
#16
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/29737566/phosphorylated-%C3%AE-synuclein-in-the-retina-is-a-biomarker-of-parkinson-s-disease-pathology-severity
#17
Isabel Ortuño-Lizarán, Thomas G Beach, Geidy E Serrano, Douglas G Walker, Charles H Adler, Nicolás Cuenca
BACKGROUND: PD patients often have visual alterations, for example, loss of visual acuity, contrast sensitivity or motion perception, and diminished electroretinogram responses. PD pathology is mainly characterized by the accumulation of pathological α-synuclein deposits in the brain, but little is known about how synucleinopathy affects the retina. OBJECTIVE: To study the correlation between α-synuclein deposits in the retina and brain of autopsied subjects with PD and incidental Lewy body disease...
May 8, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29724601/longstanding-disease-free-survival-in-idiopathic-rem-sleep-behavior-disorder-is-neurodegeneration-inevitable
#18
Chun Yao, Seyed-Mohammad Fereshtehnejad, Benjamin K Dawson, Amelie Pelletier, Ziv Gan-Or, Jean-François Gagnon, Jacques Y Montplaisir, Ronald B Postuma
INTRODUCTION: Studies estimate that >80% of patients with idiopathic REM sleep behavior disorder (iRBD) eventually develop parkinsonism or dementia. However, a small group remains disease-free for long periods, raising the question of whether they truly have prodromal disease. METHODS: We selected subjects with iRBD who were diagnosed at least 10 years previously, and were still disease free (longstanding iRBD) (n = 11). We compared them to 'early converters' (n = 27) defined as those who phenoconverted to parkinsonism or dementia within 4 years after diagnosis, and to age- and sex-matched healthy controls (n = 68)...
April 4, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29722892/inter-rater-agreement-for-visual-discrimination-of-phasic-and-tonic-electromyographic-activity-in-sleep
#19
Donald L Bliwise, Jacqueline Fairley, Scott Hoff, Richard S Rosenberg, David B Rye, David A Schulman, Lynn Marie Trotti
Study Objectives: The objective of this study was to determine the confidence of expert raters in discriminating phasic and tonic electromyographic (EMG) activity. We undertook this study because we suspected that even expert scorers may disagree on whether a given EMG segment contained phasic activity, tonic activity, or both. Methods: Six individuals holding either Fellowship status in the American Academy of Sleep Medicine or Board Certification in Sleep Medicine with at least 5 years' experience in interpreting polysomnography visually examined 60 segments containing EMG activity...
May 2, 2018: Sleep
https://www.readbyqxmd.com/read/29718367/increased-oxidative-stress-exacerbates-%C3%AE-synuclein-aggregation-in-vivo
#20
Owen Scudamore, Thomas Ciossek
Increasing evidence suggests a relationship between oxidative stress and α-synuclein aggregation, the primary pathological hallmark of Parkinson disease (PD). However, a direct causal relationship has not yet been established in vivo in mouse models of PD. Superoxide dismutase 2 (SOD2) is rate limiting in the antioxidant machinery of the mitochondria and even its partial deficiency elevates oxidative stress in mice. Therefore, in order to investigate a possible interaction between oxidative stress and α-synuclein aggregation in vivo, a transgenic model of PD with haplodeficiency for SOD2 was generated on the basis of the well-characterized murine (Thy-1)-h[A30P]-α-synuclein transgenic line...
April 27, 2018: Journal of Neuropathology and Experimental Neurology
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