Read by QxMD icon Read


Vassilis E Papadopoulos, Georgia Nikolopoulou, Ivi Antoniadou, Antonia Karachaliou, Giovanna Arianoglou, Evangelia Emmanouilidou, S Pablo Sardi, Leonidas Stefanis, Kostas Vekrellis
Glucocerebrosidase gene (GBA) mutations are the most common genetic contributor to Parkinson's Disease (PD) and are associated with decreased Glucocerebrosidase (GCase) enzymatic activity in PD. PD patients without GBA mutations also exhibit lower levels of GCase activity in the central nervous system (CNS) suggesting a potential contribution of the enzyme activity in disease pathogenesis, possibly by alteration of lysosomal function. α-synuclein, a protein with a central role in PD pathogenesis, has been shown to be secreted partly in association with exosomes...
March 14, 2018: Human Molecular Genetics
Chye Soi Moi, Chia Kin Yen, Khuen Yen Ng, Koh Rhun Yian
Protein misfolding and aggregation have been considered the common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). These abnormal proteins aggregation damage mitochondria and induce oxidative stress and resulting neuronal cell death. Prolong neuronal damage activates microglia and astrocytes, development of inflammation reaction and further promotes neurodegeneration. Thus, elimination of abnormal proteins aggregation without eliciting any adverse effects are the main treatment strategies...
March 15, 2018: CNS & Neurological Disorders Drug Targets
Charlotte Ridler
No abstract text is available yet for this article.
March 16, 2018: Nature Reviews. Neurology
Julia E Gerson, Kathleen M Farmer, Natalie Henson, Diana L Castillo-Carranza, Mariana Carretero Murillo, Urmi Sengupta, Alan Barrett, Rakez Kayed
BACKGROUND: We have evaluated the efficacy of targeting the toxic, oligomeric form of tau protein by passive immunotherapy in a mouse model of synucleinopathy. Parkinson's disease and Lewy body dementia are two of the most common neurodegenerative disorders and are primarily characterized by the accumulation of α-synuclein in Lewy bodies. However, evidence shows that smaller, oligomeric aggregates are likely the most toxic form of the protein. Moreover, a large body of research suggests that α-synuclein interacts with tau in disease and may act in a synergistic mechanism, implicating tau oligomers as a potential therapeutic target...
March 15, 2018: Molecular Neurodegeneration
Sara Ekmark-Lewén, Veronica Lindström, Astrid Gumucio, Elisabeth Ihse, Anish Behere, Philipp J Kahle, Eva Nordström, Maria Eriksson, Anna Erlandsson, Joakim Bergström, Martin Ingelsson
Introduction: Intraneuronal inclusions of alpha-synuclein are commonly found in the brain of patients with Parkinson's disease and other α-synucleinopathies. The correlation between alpha-synuclein pathology and symptoms has been studied in various animal models. In (Thy-1)-h[A30P] alpha-synuclein transgenic mice, behavioral and motor abnormalities were reported from 12 and 15 months, respectively. The aim of this study was to investigate whether these mice also display symptoms at earlier time points...
March 2018: Brain and Behavior
Roshan Kumar, Raniki Kumari, Sanjay Kumar, Deepak Kumar Jangir, Tushar Kanti Maiti
α-Synuclein, a major constituent of proteinaceous inclusions named Lewy body, has been shown to be released and taken up by cells, which may facilitate its progressive pathological spreading and neuronal cell death in Parkinson's disease. However, the pathophysiological effect and signalling cascade initiated by extracellular α-synuclein in cellular milieu are not well understood. Herein we have investigated the perturbations induced by low molecular weight α-synuclein and different types of α-synuclein oligomers in the neuroblastoma SH-SY5Y cells...
March 14, 2018: Biomacromolecules
Ivan Martinez-Valbuena, Irene Amat-Villegas, Rafael Valenti-Azcarate, Maria Del Mar Carmona-Abellan, Irene Marcilla, Maria-Teresa Tuñon, Maria-Rosario Luquin
Parkinson's disease patients experience a wide range of non-motor symptoms that may be provoked by deposits of phosphorylated α-synuclein in the peripheral nervous system. Pre-existing diabetes mellitus might be a risk factor for developing Parkinson's disease, and indeed, nearly 60% of Parkinson's disease patients are insulin resistant. Thus, we have investigated whether phosphorylated α-synuclein is deposited in pancreatic tissue of subjects with synucleinopathies. We studied pancreatic tissue from 39 subjects diagnosed with Parkinson's disease, Lewy body Dementia or incidental Lewy bodies disease, as well as that from 34 subjects with diabetes mellitus and a normal neuropathological examination, and 52 subjects with a normal neuropathological examination...
March 13, 2018: Acta Neuropathologica
Jatish Kumar, Hasier Eraña, Elena López-Martínez, Nathalie Claes, Víctor F Martín, Diego M Solís, Sara Bals, Aitziber L Cortajarena, Joaquín Castilla, Luis M Liz-Marzán
Amyloid fibrils, which are closely associated with various neurodegenerative diseases, are the final products in many protein aggregation pathways. The identification of fibrils at low concentration is, therefore, pivotal in disease diagnosis and development of therapeutic strategies. We report a methodology for the specific identification of amyloid fibrils using chiroptical effects in plasmonic nanoparticles. The formation of amyloid fibrils based on α-synuclein was probed using gold nanorods, which showed no apparent interaction with monomeric proteins but effective adsorption onto fibril structures via noncovalent interactions...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Vincenzo Donadio
No abstract text is available yet for this article.
March 13, 2018: Neurology
Imran Khan
No abstract text is available yet for this article.
March 13, 2018: Neurology
Chafic Karam, Steven Galetta
No abstract text is available yet for this article.
March 13, 2018: Neurology
José A Del Río, Isidre Ferrer, Rosalina Gavín
Several studies have indicated that certain misfolded amyloids composed of tau, β-amyloid or α-synuclein can be transferred from cell to cell, suggesting the contribution of mechanisms reminiscent of those by which infective prions spread through the brain. This process of a 'prion-like' spreading between cells is also relevant as a novel putative therapeutic target that could block the spreading of proteinaceous aggregates throughout the brain which may underlie the progressive nature of neurodegenerative diseases...
March 9, 2018: Progress in Neurobiology
Yi-Qi Lin, Sheng-Di Chen
Increasing evidence indicates a strong association between rapid eye movement sleep behavior disorder (RBD) and Parkinson's disease - cognitive impairment (PD-CI). Numerous longitudinal and cross-sectional studies have shown that RBD may be an important risk factor and predictor of Parkinson's disease - mild cognitive impairment (PD-MCI) and Parkinson's disease dementia (PDD); which may be explained by the association of mechanisms between RBD and PD-CI, including neurotransmitter alterations, genetic mutation, neuroinflammation, alpha-synuclein inclusion, abnormal cerebral metabolism and cortical activity slowing...
April 2018: Sleep Medicine
Or Szekely, Gregory Lars Olsen, Isabella Caterina Felli, Lucio Frydman
This study demonstrates the usefulness derived from relying on hyperpolarized water obtained by dissolution DNP, for site-resolved biophysical NMR studies of intrinsically disordered proteins. Thanks to the facile amide-solvent exchange experienced by protons in these proteins, 2D NMR experiments that like HMQC rely on the polarization of the amide protons, can be enhanced using hyperpolarized water by several orders of magnitude over their conventional counterparts. Optimizations of the DNP procedure and of the subsequent injection into the protein sample are necessary to achieve these gains while preserving state-of-the-art resolution; procedures enabling this transfer of the hyperpolarized water and the achievement of foamless hyperpolarized protein solutions, are here demonstrated...
March 12, 2018: Analytical Chemistry
Sing-Hui Ong, Kai-Wey Goh, Cornelius Kwang-Lee Chieng, Yee-How Say
Background: Tumor-induced angiogenesis is an imperative event in pledging new vasculature for tumor metastasis. Since overexpression of neuronal proteins gamma-synuclein (γ-Syn) and cellular prion protein (PrPC ) is always detected in advanced stages of cancer diseases which involve metastasis, this study aimed to investigate whether γ-Syn or PrPC overexpression in colorectal adenocarcinoma, LS 174T cells affects angiogenesis of endothelial cells, EA.hy 926 (EA). Methods: EA cells were treated with conditioned media (CM) of LS 174T-γ-Syn or LS 174T-PrP, and their proliferation, invasion, migration, adhesion and ability to form angiogenic tubes were assessed using a range of biological assays...
2018: PeerJ
Hector R Mendez-Gomez, Jasbir Singh, Craig Meyers, Weijun Chen, Oleg S Gorbatyuk, Nicholas Muzyczka
Phospholipase D2 (PLD2), an enzyme involved in vesicle trafficking and membrane signaling, interacts with α-synuclein, a protein known to contribute in the development of Parkinson disease. We previously reported that PLD2 overexpression in rat substantia nigra pars compacta (SNc) causes a rapid neurodegeneration of dopamine neurons, and that α-synuclein suppresses PLD2-induced nigral degeneration (Gorbatyuk et al., 2010). Here, we report that PLD2 toxicity is due to its lipase activity. Overexpression of a catalytically inactive mutant (K758R) of PLD2 prevents the loss of dopaminergic neurons in the SNc and does not show signs of toxicity after 10 weeks of overexpression...
March 8, 2018: Neuroscience
Emma Robson, Clare Tweedy, Nelson Manzanza, John-Paul Taylor, Peter Atkinson, Fiona Randall, Amy Reeve, Gavin J Clowry, Fiona E N LeBeau
Intracellular accumulation of alpha-synuclein (α-syn) is a key pathological process evident in Lewy body dementias (LBD), including Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). LBD results in marked cognitive impairments and changes in cortical networks. To assess the impact of abnormal α-syn expression on cortical network oscillations relevant to cognitive function, we studied changes in fast beta/gamma network oscillations in the hippocampus in a mouse line that over-expresses human mutant α-syn (A30P)...
March 7, 2018: Neuroscience
Alex Yen-Yu Chen, Tim Tully
Parkinson's disease (PD) is a progressive motor neurodegenerative disorder, characterized by a selective loss of dopaminergic neurons in the substantia nigra. The complexity of disease etiology includes both genetic and environmental factors. No effective drug that can modify disease progression and protect dopamine neurons from degeneration is presently available. Human α-Synuclein A30P (A30P) is a mutant gene identified in early onset PD and showed to result selective dopamine neuron loss in transgenic A30P flies and mice...
March 7, 2018: Neurobiology of Disease
Paolo Ruzza, Rosa Maria Vitale, Rohanah Hussain, Alessia Montini, Claudia Honisch, Alice Pozzebon, Charlotte S Hughes, Barbara Biondi, Pietro Amodeo, GianPietro Sechi, Giuliano Siligardi
BACKGROUND: Lysozyme is a widely distributed enzyme present in a variety of tissue and body fluids. Human and hen egg white lysozyme are used as validated model to study protein folding and stability and to understand protein misfolding and aggregation. We recently found that ceftriaxone, a β-lactam antibiotic able to overcome the blood-brain barrier, successfully eliminated the cellular toxic effects of misfolded proteins as Glial Fibrillary Acidic Protein and α-synuclein. To further understand the anti-amyloidogenic properties of ceftriaxone, we studied its activity towards lysozyme aggregation with the aim to investigate a possible chaperone-like activity of this molecule...
March 7, 2018: Biochimica et Biophysica Acta
Rakesh Kumar, Subhadeep Das, Ganesh M Mohite, Saroj K Rout, Saayak Halder, Narendra Nath Jha, Soumik Ray, Surabhi Mehra, Vipin Agarwal, Samir K Maji
α-synuclein (α-Syn) aggregation is associated with Parkinson's disease (PD) pathogenesis. In PD, the role of oligomer versus fibrils in neuronal cell death is debatable but recent studies suggest oligomers are a proximate neurotoxin. Here, we show that soluble α-Syn monomers convert from solution to gel state on incubation at high concentration that might be relevant to PD-associated local increase in α-Syn concentration. A detailed characterization of the gel showed co-existence of monomers, oligomers and short fibrils...
March 10, 2018: Angewandte Chemie
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"