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https://www.readbyqxmd.com/read/28728000/tailor-made-purified-human-platelet-lysate-concentrated-in-neurotrophins-for-treatment-of-parkinson-s-disease
#1
Ming-Li Chou, Joe-Wei Wu, Flore Gouel, Aurélie Jonneaux, Kelly Tillerman, Ting-Yi Renn, Charlotte Laloux, Hung-Ming Chang, Liang-Tzung Lin, Jean-Christophe Devedjian, David Devos, Thierry Burnouf
Human platelet lysates (PLs), which contain multiple neurotrophins, have been proposed for treating neurodegenerative disorders, including Parkinson's disease (PD). However, current PLs suspended in plasma have high protein content and contain fibrinogen/fibrin and, following activation, also proteolytic and thrombogenic enzymes. Upon brain administration, such PLs may saturate the cerebrospinal fluid and exert neurotoxicity. We assessed whether purified PLs, concentrated in neurotrophins, protected dopaminergic neurons in PD models...
July 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28726848/patch-clamp-technique-to-characterize-ion-channels-in-enlarged-individual-endolysosomes
#2
Cheng-Chang Chen, Chunlei Cang, Stefanie Fenske, Elisabeth Butz, Yu-Kai Chao, Martin Biel, Dejian Ren, Christian Wahl-Schott, Christian Grimm
According to proteomics analyses, more than 70 different ion channels and transporters are harbored in membranes of intracellular compartments such as endosomes and lysosomes. Malfunctioning of these channels has been implicated in human diseases such as lysosomal storage disorders, neurodegenerative diseases and metabolic pathologies, as well as in the progression of certain infectious diseases. As a consequence, these channels have engendered very high interest as future drug targets. Detailed electrophysiological characterization of intracellular ion channels is lacking, mainly because standard methods to analyze plasma membrane ion channels, such as the patch-clamp technique, are not readily applicable to intracellular organelles...
August 2017: Nature Protocols
https://www.readbyqxmd.com/read/28726057/macrophage-migration-inhibitory-factor-mif-modulates-trophic-signaling-through-interaction-with-serine-protease-htra1
#3
Åsa Fex Svenningsen, Svenja Löring, Anna Lahn Sørensen, Ha Uyen Buu Huynh, Simone Hjæresen, Nellie Martin, Jesper Bonnet Moeller, Maria Louise Elkjær, Uffe Holmskov, Zsolt Illes, Malin Andersson, Solveig Beck Nielsen, Eirikur Benedikz
Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cellular level. It is upregulated in neurodegenerative diseases and cancer although its function is far from clear. Here, we report the finding of a new binding partner to MIF, the serine protease HTRA1. This enzyme cleaves several growth factors, extracellular matrix molecules and is implicated in some of the same diseases as MIF...
July 19, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28726050/a-single-center-study-a%C3%AE-42-p-tau181-csf-ratio-to-discriminate-ad-from-ftd-in-clinical-setting
#4
Andrea Vergallo, Cecilia Carlesi, Cristina Pagni, Filippo Sean Giorgi, Filippo Baldacci, Lucia Petrozzi, Roberto Ceravolo, Gloria Tognoni, Gabriele Siciliano, Ubaldo Bonuccelli
Abnormal levels of beta amyloid (Aβ42) and tau protein concentrations in the cerebral spinal fluid (CSF) have been largely described in Alzheimer's disease (AD). Thus, CSF analysis of these biomarkers has been incorporated in recent AD diagnostic criteria, and it is increasingly performed for neurodegenerative dementia diagnostic workout in clinical setting. Nevertheless, the precise biomarkers CSF features in neurodegenerative dementia, either AD or Frontotemporal dementia (FTD), are still not fully clear today...
July 19, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28725954/proteasome-stress-triggers-death-of-sh-sy5y-and-t98g-cells-via-different-cellular-mechanisms
#5
Ivana Pilchova, Katarina Klacanova, Katarina Dibdiakova, Simona Saksonova, Andrea Stefanikova, Eva Vidomanova, Lucia Lichardusova, Jozef Hatok, Peter Racay
Overload or dysfunction of ubiquitin-proteasome system (UPS) is implicated in mechanisms of neurodegeneration associated with neurodegenerative diseases, e.g. Parkinson and Alzheimer disease, and ischemia-reperfusion injury. The aim of this study was to investigate the possible association between viability of neuroblastoma SH-SY5Y and glioblastoma T98G cells treated with bortezomib, inhibitor of 26S proteasome, and accumulation of ubiquitin-conjugated proteins with respect to direct cytotoxicity of aggregates of ubiquitin-conjugated proteins...
July 19, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28725179/fine-tuning-er-stress-signal-transducers-to-treat-amyotrophic-lateral-sclerosis
#6
Danilo B Medinas, Jose V González, Paulina Falcon, Claudio Hetz
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motoneurons and paralysis. The mechanisms underlying neuronal degeneration in ALS are starting to be elucidated, highlighting disturbances in motoneuron proteostasis. Endoplasmic reticulum (ER) stress has emerged as an early pathogenic event underlying motoneuron vulnerability and denervation in ALS. Maintenance of ER proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28724527/the-spread-of-prion-like-proteins-by-lysosomes-and-tunneling-nanotubes-implications-for-neurodegenerative-diseases
#7
REVIEW
Guiliana Soraya Victoria, Chiara Zurzolo
Progression of pathology in neurodegenerative diseases is hypothesized to be a non-cell-autonomous process that may be mediated by the productive spreading of prion-like protein aggregates from a "donor cell" that is the source of misfolded aggregates to an "acceptor cell" in which misfolding is propagated by conversion of the normal protein. Although the proteins involved in the various diseases are unrelated, common pathways appear to be used for their intercellular propagation and spreading. Here, we summarize recent evidence of the molecular mechanisms relevant for the intercellular trafficking of protein aggregates involved in prion, Alzheimer's, Huntington's, and Parkinson's diseases...
July 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28724458/clinical-and-therapeutic-potential-of-protein-kinase-pkr-in-cancer-and-metabolism
#8
M B Garcia-Ortega, G J Lopez, G Jimenez, J A Garcia-Garcia, V Conde, H Boulaiz, E Carrillo, M Perán, J A Marchal, M A Garcia
The protein kinase R (PKR, also called EIF2AK2) is an interferon-inducible double-stranded RNA protein kinase with multiple effects on cells that plays an active part in the cellular response to numerous types of stress. PKR has been extensively studied and documented for its relevance as an antiviral agent and a cell growth regulator. Recently, the role of PKR related to metabolism, inflammatory processes, cancer and neurodegenerative diseases has gained interest. In this review, we summarise and discuss the involvement of PKR in several cancer signalling pathways and the dual role that this kinase plays in cancer disease...
July 20, 2017: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/28724388/o-glcnac-regulation-of-autophagy-and-%C3%AE-synuclein-homeostasis-implications-for-parkinson-s-disease
#9
Willayat Y Wani, Xiaosen Ouyang, Gloria A Benavides, Matthew Redmann, Stacey S Cofield, John J Shacka, John C Chatham, Victor Darley-Usmar, Jianhua Zhang
Post-translational modification on protein Ser/Thr residues by O-linked attachment of ß-N-acetyl-glucosamine (O-GlcNAcylation) is a key mechanism integrating redox signaling, metabolism and stress responses. One of the most common neurodegenerative diseases that exhibit aberrant redox signaling, metabolism and stress response is Parkinson's disease, suggesting a potential role for O-GlcNAcylation in its pathology. To determine whether abnormal O-GlcNAcylation occurs in Parkinson's disease, we analyzed lysates from the postmortem temporal cortex of Parkinson's disease patients and compared them to age matched controls and found increased protein O-GlcNAcylation levels...
July 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28724366/predicting-progression-of-mild-cognitive-impairment-to-dementia-using-neuropsychological-data-a-supervised-learning-approach-using-time-windows
#10
Telma Pereira, Luís Lemos, Sandra Cardoso, Dina Silva, Ana Rodrigues, Isabel Santana, Alexandre de Mendonça, Manuela Guerreiro, Sara C Madeira
BACKGROUND: Predicting progression from a stage of Mild Cognitive Impairment to dementia is a major pursuit in current research. It is broadly accepted that cognition declines with a continuum between MCI and dementia. As such, cohorts of MCI patients are usually heterogeneous, containing patients at different stages of the neurodegenerative process. This hampers the prognostic task. Nevertheless, when learning prognostic models, most studies use the entire cohort of MCI patients regardless of their disease stages...
July 19, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/28724340/pharmacological-therapeutics-in-friedreich-ataxia-the-present-state
#11
Cassandra Strawser, Kimberly Schadt, Lauren Hauser, Ashley McCormick, Mckenzie Wells, Jane Larkindale, Hong Lin, David R Lynch
Friedreich ataxia (FRDA) is a progressive, inherited, neurodegenerative disease for which there is currently no cure or approved treatment. FRDA is caused by deficits in the production and expression of frataxin, a protein found in the mitochondria that is most likely responsible for regulating iron-sulfur cluster enzymes within the cell. A decrease in frataxin causes dysfunction of adenosine triphosphate synthesis, accumulation of mitochondrial iron, and other events leading to downstream cellular dysfunction...
July 20, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28723617/small-molecular-floribundiquinone-b-derived-from-medicinal-plants-inhibits-acetylcholinesterase-activity
#12
Bing Niu, Mengying Zhang, Pu Du, Li Jiang, Rui Qin, Qiang Su, Fuxue Chen, Dongshu Du, Yilai Shu, Kuo-Chen Chou
Being a neurodegenerative disorder, Alzheimer's disease (AD) is the one of the most terrible diseases. And acetylcholinesterase (AChE) is considered as an important target for treating AD. Acetylcholinesterase inhibitors (AChEI) are considered to be one of the effective drugs for the treatment of AD. The aim of this study is to find a novel potential AChEI as a drug for the treatment of AD. In this study, instead of using the synthetic compounds, we used those extracted from plants to investigate the interaction between floribundiquinone B (FB) and AChE by means of both the experimental approach such as fluorescence spectra, ultraviolet-visible (UV-vis) absorption spectrometry, circular dichroism (CD) and the theoretical approaches such as molecular docking...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723413/multifunctional-molecule-erp57-from-cancer-to-neurodegenerative-diseases
#13
REVIEW
Aubryanna Hettinghouse, Ronghan Liu, Chuan-Ju Liu
The protein disulfide isomerase (PDI) gene family is a protein family classically characterized by endoplasmic reticulum (ER) localization and isomerase and redox activity. ERp57, a prominent multifunctional member of the PDI family, is detected at various levels in multiple cellular localizations outside of the ER. ERp57 has been functionally linked to a host of physiological processes and numerous studies have demonstrated altered expression and aberrant functionality of ERp57 in association with diverse pathological states...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28722709/regulation-of-inflammation-by-microbiota-interactions-with-the-host
#14
REVIEW
J Magarian Blander, Randy S Longman, Iliyan D Iliev, Gregory F Sonnenberg, David Artis
The study of the intestinal microbiota has begun to shift from cataloging individual members of the commensal community to understanding their contributions to the physiology of the host organism in health and disease. Here, we review the effects of the microbiome on innate and adaptive immunological players from epithelial cells and antigen-presenting cells to innate lymphoid cells and regulatory T cells. We discuss recent studies that have identified diverse microbiota-derived bioactive molecules and their effects on inflammation within the intestine and distally at sites as anatomically remote as the brain...
July 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28722658/the-golgi-localized-gamma-ear-containing-arf-binding-gga-protein-family-alters-alpha-synuclein-%C3%AE-syn-oligomerization-and-secretion
#15
Bjoern von Einem, Judith Eschbach, Martin Kiechle, Anke Wahler, Dietmar R Thal, Pamela J McLean, Jochen H Weishaupt, Albert C Ludolph, Christine A F von Arnim, Karin M Danzer
Several age-related neurodegenerative disorders are associated with protein misfolding and aggregation of toxic peptides. α-synuclein (α-syn) aggregation and the resulting cytotoxicity is a hallmark of Parkinson's disease (PD) as well as dementia with Lewy bodies. Rising evidence points to oligomeric and pre-fibrillar forms as the pathogenic species, and oligomer secretion seems to be crucial for the spreading and progression of PD pathology. Recent studies implicate that dysfunctions in endolysosomal/autophagosomal pathways increase α-syn secretion...
July 15, 2017: Aging
https://www.readbyqxmd.com/read/28722507/polyglutamine-tracts-regulate-autophagy
#16
Avraham Ashkenazi, Carla F Bento, Thomas Ricketts, Mariella Vicinanza, Farah Siddiqi, Mariana Pavel, Ferdinando Squitieri, Maarten C Hardenberg, Sara Imarisio, Fiona M Menzies, David C Rubinsztein
Expansions of polyglutamine (polyQ) tracts in different proteins cause 9 neurodegenerative conditions, such as Huntington disease and various ataxias. However, many normal mammalian proteins contain shorter polyQ tracts. As these are frequently conserved in multiple species, it is likely that some of these polyQ tracts have important but unknown biological functions. Here we review our recent study showing that the polyQ domain of the deubiquitinase ATXN3/ataxin-3 enables its interaction with BECN1/beclin 1, a key macroautophagy/autophagy initiator...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28722340/a-novel-small-molecule-inhibitor-of-prion-replication-and-mutant-prion-protein-toxicity
#17
Tania Massignan, Valeria Sangiovanni, Silvia Biggi, Claudia Stincardini, Saioa R Elezgarai, Giulia Maietta, Ivan A Andreev, Nina K Ratmanova, Dmitry S Belov, Evgeny R Lukyanenko, Grigory M Belov, Maria Letizia Barreca, Andrea Altieri, Alexander V Kurkin, Emiliano Biasini
Prion diseases are a class of neurodegenerative disorders characterized by the accumulation in the brain of a self-replicating, misfolded isoform (PrPSc) of the cellular prion protein (PrPC), a cell-surface glycoprotein of uncertain function. Emerging evidence suggests that PrPC may passively serve as a substrate for the replication of PrPSc, and actively transduce its toxic effects to neuronal cells. The vast majority of previous drug screening campaigns have only targeted PrPSc replication, with largely unsuccessful results...
July 19, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28721824/potential-anti-inflammatory-effects-of-hesperidin-from-the-genus-citrus
#18
Silvia Tejada, Samuel Pinya, Miquel Martorell, Xavier Capó, Josep A Tur, Antoni Pons, Antoni Sureda
The benefits of the Mediterranean diet for protecting against many diseases are usually attributed to high consumption of certain foods, characterized by the presence of bioactive substances such as polyphenols. Citrus fruits, which are cultivated and consumed worldwide, are typical products of the Mediterranean diet. Inflammation plays an important role in the pathogenesis of numerous diseases such as arthritis, allergies and neurodegenerative disorders, among others. Dietary polyphenols constitute a large family of bioactive substances with potential beneficial effects against a broad group of diseases...
July 18, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28721823/genetic-risk-factors-for-glaucoma-and-exfoliation-syndrome-identified-by-genome-wide-association-studies
#19
Yoichi Sakurada, Fumihiko Mabuchi
Glaucoma is a neurodegenerative disease characterized by the progressive loss of retinal ganglion cells and optic nerve axons. According to its anatomical features, glaucoma is mainly subdivided into primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Exfoliation syndrome (XFS) and glaucoma (XFG) are characterized by the accumulation of extracellular materials in ocular tissues, particularly the lens surface and pupillary border. In addition to the two major forms of glaucoma, XFG is the most common cause of secondary open-angle glaucoma...
July 18, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28721811/moving-to-the-rhythm-with-clock-circadian-genes-autophagy-mtor-and-sirt1-in-degenerative-disease-and-cancer
#20
Kenneth Maiese
BACKGROUND: The mammalian circadian clock and its associated clock genes are increasingly be recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease. METHODS: In light of the significant role circadian rhythm can hold over the body's normal physiology as well as disease processes, we examined and discussed the impact circadian rhythm and clock genes hold over lifespan, neurodegenerative disorders, and tumorigenesis...
July 17, 2017: Current Neurovascular Research
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