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https://www.readbyqxmd.com/read/29906669/generation-of-gene-corrected-ipsc-line-from-parkinson-s-disease-patient-ipsc-line-with-alpha-snca-a53t-mutation
#1
Seo-Young Lee, SangKyun Jeong, Janghwan Kim, Sun-Ku Chung
Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. PD can result from a mutation of alpha-synuclein (α-SNCA), such as α-SNCA A53T. Using episomal vectors, induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts with the α-SNCA A53T mutation. A huge bacterial artificial chromosome (BAC) harboring the normal α-SNCA gene successfully corrected the α-SNCA A53T-mutant iPSCs. Melting curve analysis for allelic composition indicated that the BAC DNA was precisely targeted to the α-SNCA A53T mutation allele, without random integration...
June 9, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29901990/increased-brain-exposure-of-an-alpha-synuclein-fibrillization-modulator-by-utilization-of-an-activated-ester-pro-drug-strategy
#2
Andrew Gerard Cairns, Ana Vazquez-Romero, Mohammad Mahdi-Moein, Jörgen Åden, Charles S Elmore, Akihiro Takano, Ryosuke Arakawa, Andrea Varrone, Fredrik Almqvist, Magnus Schou
Previous work in our laboratories has identified a series of peptidomimetic 2-pyridone molecules as modulators of alpha synuclein (α-syn) fibrillization in vitro. As a first step towards developing molecules from this scaffold as PET imaging agents, we were interested in evaluating their BBB permeability in non-human primates (NHP) in vivo. For this purpose, 2-pyridone 12 was prepared and found to accelerate -syn fibrillization in vitro. Acid 12, and its acetoxymethyl ester analog 14, were then radiolabeled with 11C (t1/2=20...
June 14, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29896411/glucocerebrosidase-mrna-is-diminished-in-brain-of-lewy-body-diseases-and-changes-with-disease-progression-in-blood
#3
Laia Perez-Roca, Cristina Adame-Castillo, Jaume Campdelacreu, Lourdes Ispierto, Dolores Vilas, Ramon Rene, Ramiro Alvarez, Jordi Gascon-Bayarri, Maria A Serrano-Munoz, Aurelio Ariza, Katrin Beyer
Parkinson disease (PD) and dementia with Lewy bodies (DLB) are Lewy body diseases characterized by abnormal alpha-synuclein deposits and overlapping pathological features in the brain. Several studies have shown that glucocerebrosidase (GBA) deficiency is involved in the development of LB diseases. Here, we aimed to find out if this deficiency starts at the transcriptional level, also involves alternative splicing, and if GBA expression changes in brain are also detectable in blood of patients with LB diseases...
April 2018: Aging and Disease
https://www.readbyqxmd.com/read/29888671/effect-of-capsaicin-on-the-oxidative-stress-and-dopamine-content-in-the-transgenic-drosophila-model-of-parkinson-s-disease
#4
Yasir H Siddique, Falaq Naz, Smita Jyoti
In the present study the effect of capsaicin was studied on PD model flies expressing human alpha synuclein. First the potential of scavenging superoxide anion and free radicals by capsaicin at doses of 20, 40, 80 and 100 μM was estimated. The PD flies were allowed to feed separately on the diet containg 20, 40, 80 and 100 μM of capsaicin, respectively, for 24 days. After 24 days of exposure, fly head homogenate was prepared from each group and was used to estimate glutathione (GSH), protein carbonyl (PC), dopamine content, lipid peroxidation (LPO), glutathione-S-transferase (GST) and monoamine oxidase (MAO) activity...
June 2018: Acta Biologica Hungarica
https://www.readbyqxmd.com/read/29886527/generation-and-characterization-of-stable-%C3%AE-synuclein-oligomers
#5
Leire Almandoz-Gil, Martin Ingelsson, Joakim Bergström
Alpha-synuclein oligomers are linked to the pathogenesis of Parkinson's disease and related neurodegenerative diseases. In this chapter, we present a method to generate kinetically stable α-synuclein oligomers by the addition of reactive aldehydes, 4-hydroxy-2-nonenal, and 4-oxo-2-nonenal. We also describe biochemical and immunological techniques to characterize the generated oligomers.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29883833/rapid-eye-movement-sleep-behavior-disorder-and-the-link-to-alpha-synucleinopathies
#6
REVIEW
Daniel A Barone, Claire Henchcliffe
Rapid eye movement (REM) sleep behavior disorder (RBD) involves REM sleep without atonia in conjunction with a recurrent nocturnal dream enactment behavior, with vocalizations such as shouting and screaming, and motor behaviors such as punching and kicking. Secondary RBD is well described in association with neurological disorders including Parkinson's disease (PD), multiple system atrophy (MSA), and other conditions involving brainstem structures such as tumors. However, RBD alone is now considered to be a potential harbinger of later development of neurodegenerative disorders, in particular PD, MSA, dementia with Lewy bodies (DLB), and pure autonomic failure...
May 29, 2018: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/29882798/microbiome-gut-brain-axis-and-toll-like-receptors-in-parkinson-s-disease
#7
REVIEW
Valentina Caputi, Maria Cecilia Giron
Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disease characterized by α-synucleinopathy, which involves all districts of the brain-gut axis, including the central, autonomic and enteric nervous systems. The highly bidirectional communication between the brain and the gut is markedly influenced by the microbiome through integrated immunological, neuroendocrine and neurological processes. The gut microbiota and its relevant metabolites interact with the host via a series of biochemical and functional inputs, thereby affecting host homeostasis and health...
June 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29868450/regional-expression-of-genes-mediating-trans-synaptic-alpha-synuclein-transfer-predicts-regional-atrophy-in-parkinson-disease
#8
Benjamin Freeze, Diana Acosta, Sneha Pandya, Yize Zhao, Ashish Raj
Multiple genes have been implicated in Parkinson disease pathogenesis, but the relationship between regional expression of these genes and regional dysfunction across the brain is unknown. We address this question by joint analysis of high resolution magnetic resonance imaging data from the Parkinson's Progression Markers Initiative and regional genetic microarray expression data from the Allen Brain Atlas. Regional brain atrophy and genetic expression was co-registered to a common 86 region brain atlas and robust multivariable regression analysis was performed to identify genetic predictors of regional brain atrophy...
2018: NeuroImage: Clinical
https://www.readbyqxmd.com/read/29867358/the-exosomal-total-%C3%AE-synuclein-ratio-in-plasma-is-associated-with-glucocerebrosidase-activity-and-correlates-with-measures-of-disease-severity-in-pd-patients
#9
Silvia Cerri, Cristina Ghezzi, Maria Sampieri, Francesca Siani, Micol Avenali, Gianluca Dornini, Roberta Zangaglia, Brigida Minafra, Fabio Blandini
Intensive research efforts in the field of Parkinson's disease (PD) are focusing on identifying reliable biomarkers which possibly help physicians in predicting disease onset, diagnosis, and progression as well as evaluating the response to disease-modifying treatments. Given that abnormal alpha-synuclein (α-syn) accumulation is a primary component of PD pathology, this protein has attracted considerable interest as a potential biomarker for PD. Alpha-synuclein can be detected in several body fluids, including plasma, where it can be found as free form or in association with exosomes, small membranous vesicles secreted by virtually all cell types...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29866603/salivary-biomarkers-for-the-diagnosis-and-monitoring-of-neurological-diseases
#10
REVIEW
Raymond Farah, Hayat Haraty, Ziad Salame, Youssef Fares, David M Ojcius, Najwane Said Sadier
Current research efforts on neurological diseases are focused on identifying novel disease biomarkers to aid in diagnosis, provide accurate prognostic information and monitor disease progression. With advances in detection and quantification methods in genomics, proteomics and metabolomics, saliva has emerged as a good source of samples for detection of disease biomarkers. Obtaining a sample of saliva offers multiple advantages over the currently tested biological fluids as it is a non-invasive, painless and simple procedure that does not require expert training or harbour undesirable side effects for the patients...
April 2018: Biomedical Journal
https://www.readbyqxmd.com/read/29850516/significant-changes-in-plasma-alpha-synuclein-and-beta-synuclein-levels-in-male-children-with-autism-spectrum-disorder
#11
Wilaiwan Sriwimol, Pornprot Limprasert
Alpha-synuclein ( α -synuclein) and beta-synuclein ( β -synuclein) are presynaptic proteins playing important roles in neuronal plasticity and synaptic vesicle regulation. To evaluate the association of these two proteins and autism spectrum disorder (ASD), we investigated the plasma α -synuclein and β -synuclein levels in 39 male children with ASD (2 subgroups: 25 autism and 14 pervasive developmental disorder-not otherwise specified (PDD-NOS)) comparing with 29 sex- and age-matched controls by using enzyme-linked immunosorbent assay (ELISA)...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29843738/correction-to-lewy-body-like-alpha-synuclein-inclusions-trigger-reactive-microgliosis-prior-to-nigral-degeneration
#12
Megan F Duffy, Timothy J Collier, Joseph R Patterson, Christopher J Kemp, Kelvin C Luk, Malú G Tansey, Katrina L Paumier, Nicholas M Kanaan, D Luke Fischer, Nicole K Polinski, Olivia L Barth, Jacob W Howe, Nishant N Vaikath, Nour K Majbour, Omar M A El-Agnaf, Caryl E Sortwell
After publication of the original article [1] it was noted that the name of author, D. Luke Fisher, was erroneously typeset in both the PDF and online formats of the manuscript as Luke D. Fisher.
May 29, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29801501/a-novel-extended-form-of-alpha-synuclein-3-utr-in-the-human-brain
#13
Goun Je, Subhrangshu Guhathakurta, Seung Pil Yun, Han Seok Ko, Yoon-Seong Kim
Alpha-synuclein (α-SYN) is one of the key contributors in Parkinson's disease (PD) pathogenesis. Despite the fact that increased α-SYN levels are considered one of the key contributors in developing PD, the molecular mechanisms underlying the regulation of α-SYN still needs to be elucidated. Since the 3' untranslated regions (3'UTRs) of messenger RNAs (mRNAs) have important roles in translation, localization, and stability of mRNAs through RNA binding proteins (RBPs) and microRNAs (miRNAs), it is important to identify the exact length of 3'UTRs of transcripts in order to understand the precise regulation of gene expression...
May 25, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29790977/alpha-synuclein-aggregates-in-labial-salivary-glands-of-idiopathic-rapid-eye-movement-sleep-behavior-disorder
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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