keyword
MENU ▼
Read by QxMD icon Read
search

A53T

keyword
https://www.readbyqxmd.com/read/28706191/aldehyde-dehydrogenase-1-positive-nigrostriatal-dopaminergic-fibers-exhibit-distinct-projection-pattern-and-dopamine-release-dynamics-at-mouse-dorsal-striatum
#1
Carmelo Sgobio, Junbing Wu, Wang Zheng, Xi Chen, Jing Pan, Armando G Salinas, Margaret I Davis, David M Lovinger, Huaibin Cai
Aldehyde dehydrogenase 1 (ALDH1A1)-positive dopaminergic (DA) neurons at the ventral substantia nigra pars compacta (SNpc) preferentially degenerate in Parkinson's disease (PD). Their projection pattern and dopamine release properties, however, remains uncharacterized. Here we show that ALDH1A1-positive axons project predominantly to the rostral two-thirds of dorsal striatum. A portion of these axons converge on a small fraction of striosome compartments restricted to the dorsolateral striatum (DLS), where less dopamine release was measured compared to the adjacent matrix enriched with the ALDH1A1-negative axons...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698628/%C3%AE-synuclein-control-of-mitochondrial-homeostasis-in-human-derived-neurons-is-disrupted-by-mutations-associated-with-parkinson-s-disease
#2
Victorio Martin Pozo Devoto, Nicolas Dimopoulos, Matías Alloatti, María Belén Pardi, Trinidad M Saez, María Gabriela Otero, Lucas Eneas Cromberg, Antonia Marín-Burgin, Maria Elida Scassa, Gorazd B Stokin, Alejandro F Schinder, Gustavo Sevlever, Tomás Luis Falzone
The etiology of Parkinson's disease (PD) converges on a common pathogenic pathway of mitochondrial defects in which α-Synuclein (αSyn) is thought to play a role. However, the mechanisms by which αSyn and its disease-associated allelic variants cause mitochondrial dysfunction remain unknown. Here, we analyzed mitochondrial axonal transport and morphology in human-derived neurons overexpressing wild-type (WT) αSyn or the mutated variants A30P or A53T, which are known to have differential lipid affinities...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696461/room-temperature-in-cell-epr-spectroscopy-alpha-synuclein-disease-variants-remain-intrinsically-disordered-in-the-cell
#3
Julia Cattani, Vinod Subramaniam, Malte Drescher
Human alpha-Synuclein (aS), implicated in Parkinson's disease, adopts a rich variety of different conformations depending on the macromolecular context. In order to unravel its pathophysiological role, monitoring its intracellular conformational state and identifying differences for the disease variants is crucial. Here, we present an intracellular spectroscopy approach based on a systematic spin-labeling site-scan in combination with intracellular electron paramagnetic resonance spectroscopy determining conformations on a molecular scale...
July 11, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28677385/minimal-nucleation-state-of-%C3%AE-synuclein-is-stabilized-by-dynamic-threonine-water-networks
#4
Tod D Romo, Andrew K Lewis, Anthony R Braun, Alan Grossfield, Jonathan N Sachs
The first structures of α-synuclein (αSyn) fibrils have recently been solved. Here, we use a unique combination of molecular dynamics simulation strategies to address the minimal nucleation size of the 11-amino acid NAC protofibril solved by X-ray and to interrogate the dynamic behavior of unexpected crystal waters in the steric zipper. We found that protofibrils of >8 chains are thermodynamically stabilized due to protection of the fibril core from solvent influx and ordering of the end strands by the fibril core...
July 10, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28676257/baicalein-blocks-%C3%AE-synuclein-secretion-from-sn4741-cells-and-facilitates-%C3%AE-synuclein-polymerization-to-big-complex
#5
Xingjian Li, Guofeng Zhang, Qi Nie, Ting Wu, Luyan Jiao, Meige Zheng, Xiaomei Wan, Yonglin Li, Song Wu, Bin Jiang, Xianhong Xiang, Jinhai Duan, Xian Lin
The secretion of α-synuclein (α-syn) acts as an essential driver in the propagation of synucleinopathies in brain. The clearance of extracellular α-syn or blockade of the cell-to-cell transmission of α-syn is a promising approach to prohibiting synucleinopathies propagation. Baicalein (BAI), a flavonoid from Chinese herb, has been reported to bind covalently to α-syn to inhibit α-syn fibrillation and degrade its fibrils. However, whether BAI inhibits α-syn secretion is unclear. Here we showed that BAI reduced α-syn in the media of dopaminergic cell lines (SN4741) overexpressing wild-type α-syn (W-syn) or A53T mutant type α-syn (A53T-syn), while increased α-syn expression in cell lysates, upregulated the cell viability and increased the ratio of LC3 II/LC3 I, the latter is an indicator reflects the macroautophagic level...
July 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28673739/sirtuin-3-rescues-neurons-through-the-stabilisation-of-mitochondrial-biogenetics-in-the-virally-expressing-mutant-%C3%AE-synuclein-rat-model-of-parkinsonism
#6
Jacqueline A Gleave, Lindsay R Arathoon, Dennison Trinh, Kristin E Lizal, Nicolas Giguère, James H M Barber, Zainab Najarali, M Hassan Khan, Sherri L Thiele, Mahin S Semmen, James B Koprich, Jonathan M Brotchie, James H Eubanks, Louis-Eric Trudeau, Joanne E Nash
Parkinson's disease (PD) is a neurodegenerative movement disorder, which affects approximately 1-2% of the population over 60years of age. Current treatments for PD are symptomatic, and the pathology of the disease continues to progresses over time until palliative care is required. Mitochondria are key players in the pathology of PD. Genetic and post mortem studies have shown a large number of mitochondrial abnormalities in the substantia nigra pars compacta (SNc) of the parkinsonian brain. Furthermore, physiologically, mitochondria of nigral neurons are constantly under unusually high levels of metabolic stress because of the excitatory properties and architecture of these neurons...
July 1, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28671665/asparagine-endopeptidase-cleaves-%C3%AE-synuclein-and-mediates-pathologic-activities-in-parkinson-s-disease
#7
Zhentao Zhang, Seong Su Kang, Xia Liu, Eun Hee Ahn, Zhaohui Zhang, Li He, P Michael Iuvone, Duc M Duong, Nicholas T Seyfried, Matthew J Benskey, Fredric P Manfredsson, Lingjing Jin, Yi E Sun, Jian-Zhi Wang, Keqiang Ye
Aggregated forms of α-synuclein play a crucial role in the pathogenesis of synucleinopathies such as Parkinson's disease (PD). However, the molecular mechanisms underlying the pathogenic effects of α-synuclein are not completely understood. Here we show that asparagine endopeptidase (AEP) cleaves human α-synuclein, triggers its aggregation and escalates its neurotoxicity, thus leading to dopaminergic neuronal loss and motor impairments in a mouse model. AEP is activated and cleaves human α-synuclein at N103 in an age-dependent manner...
July 3, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28637871/phosphorylation-at-serine-31-targets-tyrosine-hydroxylase-to-vesicles-for-transport-along-microtubules
#8
Ana Jorge-Finnigan, Rune Kleppe, Kunwar Jung-Kc, Ming Ying, Michael Marie, Ivan Rios-Mondragon, Michael F Salvatore, Jaakko Saraste, Aurora Martinez
Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine into L-Dopa, which is the rate-limiting step in the synthesis of catecholamines, particularly dopamine in dopaminergergic neurons. Low dopamine levels and death of the dopaminergic neurons are hallmarks of Parkinson's disease (PD), where α-synuclein is also a key player. TH is highly regulated, notably by phosphorylation of several Ser/Thr residues in the N-terminal tail. However, the functional role of TH phosphorylation at the Ser31 site (THpSer31) remains unclear...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28624352/pressure-effects-on-%C3%AE-synuclein-amyloid-fibrils-an-experimental-investigation-on-their-dissociation-and-reversible-nature
#9
Federica Piccirilli, Nicoletta Plotegher, Francesco Spinozzi, Luigi Bubacco, Paolo Mariani, Mariano Beltramini, Isabella Tessari, Valeria Militello, Andrea Perucchi, Heinz Amenitsch, Enrico Baldassarri, Milos Steinhart, Stefano Lupi, Maria Grazia Ortore
α-synuclein amyloid fibrils are found in surviving neurons of Parkinson's disease affected patients, but the role they play in the disease development is still under debate. A growing number of evidences points to soluble oligomers as the major cytotoxic species, while insoluble fibrillar aggregates could even play a protection role. In this work, we investigate α-synuclein fibrils dissociation induced at high pressure by means of Small Angle X-ray Scattering and Fourier Transform Infrared Spectroscopy. Fibrils were produced from wild type α-synuclein and two familial mutants, A30P and A53T...
August 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28623611/deferiprone-rescues-behavioral-deficits-induced-by-mild-iron-exposure-in-a-mouse-model-of-alpha-synuclein-aggregation
#10
Eleonora Carboni, Lars Tatenhorst, Lars Tönges, Elisabeth Barski, Vivian Dambeck, Mathias Bähr, Paul Lingor
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, and its causes remain unknown. A major hallmark of the disease is the increasing presence of aggregated alpha-synuclein (aSyn). Furthermore, there is a solid consensus on iron (Fe) accumulation in several regions of PD brains during disease progression. In our study, we focused on the interaction of Fe and aggregating aSyn in vivo in a transgenic mouse model overexpressing human aSyn bearing the A53T mutation (prnp.aSyn.A53T). We utilized a neonatal iron-feeding model to exacerbate the motor phenotype of the transgenic mouse model...
June 16, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28619113/mechanisms-underlying-extensive-ser129-phosphorylation-in-%C3%AE-synuclein-aggregates
#11
Shigeki Arawaka, Hiroyasu Sato, Asuka Sasaki, Shingo Koyama, Takeo Kato
Parkinson's disease (PD) is characterized neuropathologically by intracellular aggregates of fibrillar α-synuclein, termed Lewy bodies (LBs). Approximately 90% of α-synuclein deposited as LBs is phosphorylated at Ser129 in brains with PD. In contrast, only 4% of total α-synuclein is phosphorylated at Ser129 in brains with normal individuals. It is unclear why extensive phosphorylation occurs in the pathological process of PD. To address this issue, we investigated a mechanism and role of Ser129-phosphorylation in regulating accumulation of α-synuclein...
June 15, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28580639/mesenchymal-stem-cells-stabilize-axonal-transports-for-autophagic-clearance-of-%C3%AE-synuclein-in-parkinsonian-models
#12
Se Hee Oh, Seok Cheol Lee, Dong Yeol Kim, Ha Na Kim, Jin Young Shin, Byoung Seok Ye, Phil Hyu Lee
Genome-wide association studies have identified two loci, SNCA and the microtubule (MT)-associated protein tau, as common risk factors for Parkinson's disease (PD). Specifically, α-synuclein directly destabilizes MT via tau phosphorylation and induces axonal transport deficits that are the primary events leading to an abnormal accumulation of α-synuclein that causes nigral dopaminergic cell loss. In the present study, we demonstrated that mesenchymal stem cells (MSCs) could modulate cytoskeletal networks and trafficking to exert neuroprotective properties in wild-type or A53T α-synuclein overexpressing cells and mice...
June 5, 2017: Stem Cells
https://www.readbyqxmd.com/read/28576942/wild-type-monomeric-%C3%AE-synuclein-can-impair-vesicle-endocytosis-and-synaptic-fidelity-via-tubulin-polymerization-at-the-calyx-of-held
#13
Kohgaku Eguchi, Zacharie Taoufiq, Oliver Thorn-Seshold, Dirk Trauner, Masato Hasegawa, Tomoyuki Takahashi
α-Synuclein is a presynaptic protein the function of which has yet to be identified, but its neuronal content increases in patients of synucleinopathies including Parkinson's disease. Chronic overexpression of α-synuclein reportedly expresses various phenotypes of synaptic dysfunction, but the primary target of its toxicity has not been determined. To investigate this, we acutely loaded human recombinant α-synuclein or its pathological mutants in their monomeric forms into the calyces of Held presynaptic terminals in slices from auditorily mature and immature rats of either sex...
June 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28573674/overexpression-of-%C3%AE-synuclein-in-an-astrocyte-cell-line-promotes-autophagy-inhibition-and-apoptosis
#14
Adolfo Garcia Erustes, Fernanda Yakel Stefani, Juliana Yoshie Terashima, Roberta Sessa Stilhano, Priscila Totarelli Monteforte, Gustavo José da Silva Pereira, Sang Won Han, Andrana Karla Calgarotto, Yi-Te Hsu, Rodrigo Portes Ureshino, Cláudia Bincoletto, Soraya Soubhi Smaili
α-Synuclein is the major component of neuronal cytoplasmic aggregates called Lewy bodies, the main pathological hallmark of Parkinson disease. Although neurons are the predominant cells expressing α-synuclein in the brain, recent studies have demonstrated that primary astrocytes in culture also express α-synuclein and regulate α-synuclein trafficking. Astrocytes have a neuroprotective role in several detrimental brain conditions; we therefore analyzed the effects of the overexpression of wild-type α-synuclein and its A30P and A53T mutants on autophagy and apoptosis...
June 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28569795/cystatin-c-as-a-potential-therapeutic-mediator-against-parkinson-s-disease-via-vegf-induced-angiogenesis-and-enhanced-neuronal-autophagy-in-neurovascular-units
#15
Jing Zou, Zhaoyu Chen, Xiaobo Wei, Zhigang Chen, Yongmei Fu, Xiaoyan Yang, Dan Chen, Rui Wang, Peter Jenner, Jia-Hong Lu, Min Li, Zhuohua Zhang, Beisha Tang, Kunlin Jin, Qing Wang
Cystatin C (CYS C, Cst3) is an endogenous cysteine protease inhibitor that plays neuroprotective roles in neurodegenerative diseases. We aimed to explore the association of CYS C with Parkinson's disease (PD) models and investigate its involvement in the role of neurovascular units (NVUs) in PD neuro-pathogenesis. We used A53T α-synuclein (SNCA) transgenic mice and 6-hydroxydopamine-lesioned DAergic PC12 cells as experimental PD models to investigate the mechanisms behind this association. The injections of CYS C were administered to the right substantia nigra (SN) of A53T SNCA transgenic mice to measure the effects of CYS C in transgenic A53T SNCA mice...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28562630/the-influence-of-n-terminal-acetylation-on-micelle-induced-conformational-changes-and-aggregation-of-%C3%AE-synuclein
#16
David Ruzafa, Yuriko S Hernandez-Gomez, Giovanni Bisello, Kerensa Broersen, Bertrand Morel, Francisco Conejero-Lara
The biological function of α-Synuclein has been related to binding to lipids and membranes but these interactions can also mediate α-Synuclein aggregation, which is associated to Parkinson's disease and other neuropathologies. In brain tissue α-Synuclein is constitutively N-acetylated, a modification that plays an important role in its conformational propensity, lipid and membrane binding, and aggregation propensity. We studied the interactions of the lipid-mimetic SDS with N-acetylated and non-acetylated α-Synuclein, as well as their early-onset Parkinson's disease variants A30P, E46K and A53T...
2017: PloS One
https://www.readbyqxmd.com/read/28520872/glucocerebrosidase-deficiency-in-dopaminergic-neurons-induces-microglial-activation-without-neurodegeneration
#17
Federico N Soria, Michel Engeln, Marta Martinez-Vicente, Christelle Glangetas, María José López-González, Sandra Dovero, Benjamin Dehay, Elisabeth Normand, Miquel Vila, Alexandre Favereaux, François Georges, Christophe Lo Bianco, Erwan Bezard, Pierre-Olivier Fernagut
Mutations in the GBA1 gene encoding the lysosomal enzyme glucocerebrosidase (GBA1) are important risk factors for Parkinson's disease (PD). In vitro, altered GBA1 activity promotes alpha-synuclein accumulation while elevated levels of alpha-synuclein compromise GBA1 function, thus supporting a pathogenic mechanism in PD. However, the mechanisms by which GBA1 deficiency is linked to increased risk of PD remains elusive, partially because of lack of aged models of GBA1 deficiency. Since knocking-out GBA1 in the entire brain induces massive neurodegeneration and early death, we generated a mouse model of GBA1 deficiency amenable to investigate the long-term consequences of compromised GBA1 function in dopaminergic neurons...
May 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28482862/higher-levels-of-myelin-phospholipids-in-brains-of-neuronal-%C3%AE-synuclein-transgenic-mice-precede-myelin-loss
#18
Jessica Grigoletto, Katharina Pukaß, Ayelet Gamliel, Dana Davidi, Rachel Katz-Brull, Christiane Richter-Landsberg, Ronit Sharon
α-Synuclein is a protein involved in the pathogenesis of synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We investigated the role of neuronal α-Syn in myelin composition and abnormalities. The phospholipid content of purified myelin was determined by (31)P NMR in two mouse lines modeling PD, PrP-A53T α-Syn and Thy-1 wt-α-Syn. Significantly higher levels of phospholipids were detected in myelin purified from brains of these α-Syn transgenic mouse models than in control mice...
May 8, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28476570/expression-signatures-of-long-non-coding-rna-in-the-substantia-nigra-of-pre-symptomatic-mouse-model-of-parkinson-s-disease
#19
Fengjuan Jiao, Qingzhi Wang, Pei Zhang, Lulu Bu, Jianguo Yan, Bo Tian
Parkinson's disease (PD) is an age-dependent neurodegenerative disease that can be caused by a variety of factors. Growing evidence shows that prior to the motor phase of PD can express molecular or imaging markers. Many long non-coding RNAs (lncRNAs) have been identified in neurodegenerative disease. However, the biogenesis and function of lncRNAs in the pre-symptomatic stage of PD is poorly understood. Here, we profiled the expression of lncRNAs and mRNAs in the substantia nigra pars compacta (SNpc) of pre-symptomatic mice over-expressing human A30P*A53T α-synuclein by microarray analysis...
May 2, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28470693/subthalamic-nucleus-deep-brain-stimulation-is-neuroprotective-in-the-a53t-%C3%AE-synuclein-parkinson-s-disease-rat-model
#20
Thomas Musacchio, Maike Rebenstorff, Felix Fluri, Jonathan M Brotchie, Jens Volkmann, James B Koprich, Chi Wang Ip
OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective symptomatic therapy for motor deficits in Parkinson's disease (PD). An additional, disease-modifying effect has been suspected from studies in toxin-based PD animal models, but these models do not reflect the molecular pathology and progressive nature of PD that would be required to evaluate a disease-modifying action. Defining a disease-modifying effect could radically change the way in which DBS is used in PD...
June 2017: Annals of Neurology
keyword
keyword
82770
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"