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Lipid membrane interactions neurons

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https://www.readbyqxmd.com/read/29924993/single-molecule-characterization-of-the-interactions-between-extracellular-chaperones-and-toxic-%C3%AE-synuclein-oligomers
#1
Daniel R Whiten, Dezerae Cox, Mathew H Horrocks, Christopher G Taylor, Suman De, Patrick Flagmeier, Laura Tosatto, Janet R Kumita, Heath Ecroyd, Christopher M Dobson, David Klenerman, Mark R Wilson
The aberrant aggregation of α-synuclein is associated with several human diseases, collectively termed the α-synucleinopathies, which includes Parkinson's disease. The progression of these diseases is, in part, mediated by extracellular α-synuclein oligomers that may exert effects through several mechanisms, including prion-like transfer, direct cytotoxicity, and pro-inflammatory actions. In this study, we show that two abundant extracellular chaperones, clusterin and α2 -macroglobulin, directly bind to exposed hydrophobic regions on the surface of α-synuclein oligomers...
June 19, 2018: Cell Reports
https://www.readbyqxmd.com/read/29915373/extremely-high-frequency-electromagnetic-fields-facilitate-electrical-signal-propagation-by-increasing-transmembrane-potassium-efflux-in-an-artificial-axon-model
#2
Simona D'Agostino, Chiara Della Monica, Eleonora Palizzi, Fabio Di Pietrantonio, Massimiliano Benetti, Domenico Cannatà, Marta Cavagnaro, Dariush Sardari, Pasquale Stano, Alfonsina Ramundo-Orlando
Among the many biological effects caused by low intensity extremely high frequency electromagnetic fields (EHF-EMF) reported in the literature, those on the nervous system are a promising area for further research. The mechanisms by which these fields alter neural activity are still unclear and thus far there appears to be no frequency dependence regarding neuronal responses. Therefore, proper in vitro models for preliminary screening studies of the interaction between neural cells with EMF are needed. We designed an artificial axon model consisting of a series of parallel RC networks...
June 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29892158/modification-of-%C3%AE-synuclein-by-lipid-peroxidation-products-derived-from-polyunsaturated-fatty-acids-promotes-toxic-oligomerization-its-relevance-to-parkinson-disease
#3
REVIEW
Masayo Shamoto-Nagai, Shinsuke Hisaka, Makoto Naoi, Wakako Maruyama
Recently, toxic α-synuclein oligomer, which can mediate cell-to-cell propagation is suggested to cause sporadic Parkinson disease. α-Synuclein interacts with membrane lipids especially polyunsaturated fatty acids to stabilize its three-dementional structure. Peroxidation of polyunsaturated fatty acids may reduce their affinity to α-synuclein and peroxidation byproducts might modify α-synuclein. 4-Hydroxy-2-nonenal derived from n -6 polyunsaturated fatty acids was reported to modify α-synuclein to produce a toxic oligomer...
May 2018: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/29864134/pleomorphic-linkers-as-ubiquitous-structural-organizers-of-vesicles-in-axons
#4
Nikolas Schrod, Dimitri Vanhecke, Ulrike Laugks, Valentin Stein, Yoshiyuki Fukuda, Miroslava Schaffer, Wolfgang Baumeister, Vladan Lucic
Many cellular processes depend on a precise structural organization of molecular components. Here, we established that neurons grown in culture provide a suitable system for in situ structural investigations of cellular structures by cryo-electron tomography, a method that allows high resolution, three-dimensional imaging of fully hydrated, vitrified cellular samples. A higher level of detail of cellular components present in our images allowed us to quantitatively characterize presynaptic and cytoskeletal organization, as well as structures involved in axonal transport and endocytosis...
2018: PloS One
https://www.readbyqxmd.com/read/29792904/monoclonal-antibody-dl11c8-identifies-adam23-as-a-component-of-lipid-raft-microdomains
#5
Zaine L M Borgonovo, Caroline F Ribeiro, Michele D M Costa, Ingrid L M Souza, Gustavo R Rossi, Monica V Alcantara, Max Ingberman, Luciano G Braga, Adriana F Mercadante, Lia S Nakao, Silvio M Zanata
A disintegrin and metalloprotease protein 23 (ADAM23) is a transmembrane type I glycoprotein involved with the development and maintenance of the nervous system, including neurite outgrowth, neuronal adhesion and differentiation and regulation of synaptic transmission. In addition, ADAM23 seems to participate in immune response and tumor establishment through interaction with different members of integrin receptors. Here, we describe a novel monoclonal antibody (DL11C8) that specifically recognizes the cysteine-rich domain of both pre-protein (100kDa) and mature (70 kDa) forms of ADAM23 from different species, including human, rodents and avian orthologs...
May 21, 2018: Neuroscience
https://www.readbyqxmd.com/read/29758301/lipid-roles-in-herg-function-and-interactions-with-drugs
#6
REVIEW
Meruyert Kudaibergenova, Laura L Perissinotti, Sergei Y Noskov
Human-ether-a-go-go-related channel (hERG) is a voltage gated potassium channel (Kv 11.1) abundantly expressed in heart and brain tissues. In addition to playing an important role in mediation of repolarizing K+ currents (IKr ) in Action Potential (AP), hERG is notorious for its propensity to interact with various medications. The drug-induced block of K+ currents across hERG channel are strongly associated with dysrhythmic conditions collectively known as drug-induced long-QT-syndrome. The recent availability of the high-resolution Cryo-EM structures for the hERG channel has provided unique opportunity to resolve structural mechanisms involved into the process of voltage-gating of hERG channels, map various roles played by components of ventricular and neuronal membranes and then to connect it to cellular pathways through which diverse chemical compounds might be affecting function of the channel...
May 11, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29747825/gangliosides-in-membrane-organization
#7
Sandro Sonnino, Elena Chiricozzi, Sara Grassi, Laura Mauri, Simona Prioni, Alessandro Prinetti
Since the structure of GM1 was elucidated 55years ago, researchers have been attracted by the sialylated glycans of gangliosides. Gangliosides head groups, protruding toward the extracellular space, significantly contribute to the cell glycocalyx; and in certain cells, such as neurons, are major determinants of the features of the cell surface. Expression of glycosyltransferases involved in the de novo biosynthesis of gangliosides is tightly regulated along cell differentiation and activation, and is regarded as the main metabolic mechanism responsible for the acquisition of cell-specific ganglioside patterns...
2018: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29644863/reversible-cation-selective-attachment-and-self-assembly-of-human-tau-on-supported-brain-lipid-membranes
#8
Stefania A Mari, Susanne Wegmann, Katharina Tepper, Bradley T Hyman, Eva-Maria Mandelkow, Eckhard Mandelkow, Daniel J Müller
Misfolding and aggregation of the neuronal, microtubule-associated protein tau is involved in the pathogenesis of Alzheimer's disease and tauopathies. It has been proposed that neuronal membranes could play a role in tau release, internalization, and aggregation and that tau aggregates could exert toxicity via membrane permeabilization. Whether and how tau interacts with lipid membranes remains a matter of discussion. Here, we characterize the interaction of full-length human tau (htau40) with supported lipid membranes (SLMs) made from brain total lipid extract by time-lapse high-resolution atomic force microscopy (AFM)...
May 9, 2018: Nano Letters
https://www.readbyqxmd.com/read/29604406/interaction-of-dynamin-i-with-nap-22-a-neuronal-protein-enriched-in-the-presynaptic-region
#9
Satoko Ueno, Hiroshi Miyoshi, Yoko Maruyama, Mitsuhiro Morita, Shohei Maekawa
Neurons have well-developed membrane microdomains called "rafts" that are recovered as a detergent-resistant low-density membrane microdomain fraction (DRM). NAP-22 is one of the major protein components of neuronal DRM and localizes in the presynaptic region. In order to know the role of NAP-22 in the synaptic transmission, NAP-22 binding proteins in the cytosol were searched with an affinity screening with NAP-22 as a bait and several protein bands were detected. Using mass-analysis and western blotting, one of the main band of ∼90 kDa was identified as dynamin I...
May 14, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29580771/interactions-of-amyloid-%C3%AE-peptides-on-lipid-bilayer-studied-by-single-molecule-imaging-and-tracking
#10
Chun-Chieh Chang, Elin Edwald, Sarah Veatch, Duncan G Steel, Ari Gafni
The amyloid-β peptides (Aβ40 and Aβ42) feature prominently in the synaptic dysfunction and neuronal loss associated with Alzheimer's disease (AD). This has been proposed to be due either to interactions between Aβ and cell surface receptors affecting cell signaling, or to the formation of calcium-permeable channels in the membrane that disrupt calcium homeostasis. In both mechanisms the cell membrane is the primary cellular structure with which Aβ interacts. Aβ concentrations in human bodily fluids are very low (pM-nM) rendering studies of the size, composition, cellular binding sites and mechanism of action of the oligomers formed in vivo very challenging...
March 24, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29559883/estrogen-interactions-with-lipid-rafts-related-to-neuroprotection-impact-of-brain-ageing-and-menopause
#11
REVIEW
Raquel Marin, Mario Diaz
Estrogens (E2) exert a plethora of neuroprotective actions against aged-associated brain diseases, including Alzheimer's disease (AD). Part of these actions takes place through binding to estrogen receptors (ER) embedded in signalosomes, where numerous signaling proteins are clustered. Signalosomes are preferentially located in lipid rafts which are dynamic membrane microstructures characterized by a peculiar lipid composition enriched in gangliosides, saturated fatty acids, cholesterol, and sphingolipids. Rapid E2 interactions with ER-related signalosomes appear to trigger intracellular signaling ultimately leading to the activation of molecular mechanisms against AD...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29551631/vdac1-mitochondrial-dysfunction-and-alzheimer-s-disease
#12
REVIEW
Varda Shoshan-Barmatz, Edna Nahon-Crystal, Anna Shteinfer-Kuzmine, Rajeev Gupta
Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Although an accumulation of brain amyloid-β (Aβ) peptide and hyperphosphorylated tau protein have been implicated in the pathogenesis of AD, the etiology of the disease remains unclear. Mitochondrial dysfunction has been identified as an early event in AD pathogenesis and is reflected by reduced metabolism, disruption of Ca2+ homeostasis, and increased levels of reactive oxygen species, lipid peroxidation, and apoptosis. The focus of this review is the involvement of mitochondrial dysfunction in AD, and specifically, the role of the voltage-dependent anion channel 1 (VDAC1), which has been linked to AD pathogenesis...
May 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29526709/cause-and-consequence-of-a%C3%AE-lipid-interactions-in-alzheimer-disease-pathogenesis
#13
REVIEW
Vijayaraghavan Rangachari, Dexter N Dean, Pratip Rana, Ashwin Vaidya, Preetam Ghosh
Self-templating propagation of protein aggregate conformations is increasingly becoming a significant factor in many neurological diseases. In Alzheimer disease (AD), intrinsically disordered amyloid-β (Aβ) peptides undergo aggregation that is sensitive to environmental conditions. High-molecular weight aggregates of Aβ that form insoluble fibrils are deposited as senile plaques in AD brains. However, low-molecular weight aggregates called soluble oligomers are known to be the primary toxic agents responsible for neuronal dysfunction...
March 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29524645/inhibitory-effect-of-several-sphingolipid-metabolites-on-calcineurin
#14
Yoko Maruyama, Satoko Ueno, Mitsuhiro Morita, Fumio Hayashi, Shohei Maekawa
Neurons have well-developed membrane microdomains called "rafts" that are recovered as a detergent-resistant membrane microdomain fraction (DRM). NAP-22 is one of the major protein components of neuronal DRM. In a previous study, we showed that DRM-derived NAP-22 binds ganglioside and the inhibitory effect of ganglioside to calcineurin (CaN), a neuron-enriched calmodulin-regulated phosphoprotein phosphatase. Considering the important roles of CaN in neurons, identification of other cellular regulators of CaN could be a good clue to understand the molecular background of neuronal function...
April 23, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29514050/mechanism-of-aggregation-and-membrane-interactions-of-mammalian-prion-protein
#15
REVIEW
Sabareesan Ambadi Thody, M K Mathew, Jayant B Udgaonkar
The cellular prion protein (PrPC ), which is present ubiquitously in all mammalian neurons, is normally found to be linked to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. The conformational conversion of PrPC into misfolded and aggregated forms is associated with transmissible neurodegenerative diseases known as prion diseases. The importance of different misfolded conformations in prion diseases, and the mechanism by which prion aggregates induce neurotoxicity remain poorly understood...
March 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29491369/endoplasmic-reticulum-and-mitochondria-in-diseases-of-motor-and-sensory-neurons-a-broken-relationship
#16
REVIEW
Nathalie Bernard-Marissal, Roman Chrast, Bernard L Schneider
Recent progress in the understanding of neurodegenerative diseases revealed that multiple molecular mechanisms contribute to pathological changes in neurons. A large fraction of these alterations can be linked to dysfunction in the endoplasmic reticulum (ER) and mitochondria, affecting metabolism and secretion of lipids and proteins, calcium homeostasis, and energy production. Remarkably, these organelles are interacting with each other at specialized domains on the ER called mitochondria-associated membranes (MAMs)...
February 28, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29474891/regulation-of-kv7-2-kv7-3-channels-by-cholesterol-relevance-of-an-optimum-plasma-membrane-cholesterol-content
#17
Mayra Delgado-Ramírez, Sergio Sánchez-Armass, Ulises Meza, Aldo A Rodríguez-Menchaca
Kv7.2/Kv7.3 channels are the molecular correlate of the M-current, which stabilizes the membrane potential and controls neuronal excitability. Previous studies have shown the relevance of plasma membrane lipids on both M-currents and Kv7.2/Kv7.3 channels. Here, we report the sensitive modulation of Kv7.2/Kv7.3 channels by membrane cholesterol level. Kv7.2/Kv7.3 channels transiently expressed in HEK-293 cells were significantly inhibited by decreasing the cholesterol level in the plasma membrane by three different pharmacological strategies: methyl-β-cyclodextrin (MβCD), Filipin III, and cholesterol oxidase treatment...
February 21, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29428500/electrostatic-and-hydrophobic-interactions-of-lipid-associated-%C3%AE-synuclein-the-role-of-a-water-limited-interfaces-in-amyloid-fibrillation
#18
REVIEW
Tae Su Choi, Jong Yoon Han, Chae Eun Heo, Sun Woo Lee, Hugh I Kim
Human α‑synuclein (αSyn) is an intrinsically disordered protein (IDP) whose biological and pathological functions in brain neuronal cells have not yet been fully elucidated. αSyn intrinsically participates in aiding neurotransmitter trafficking through αSyn the association with lipid membranes. However, lipid-associated states of αSyn also induce amyloid self-assembly that is linked to the pathogenesis of various synucleinopathies. These contradicting actions arise from the limited water content near lipid-water interfaces that controls αSyn electrostatic and hydrophobic interactions...
February 8, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29408451/fluorescence-imaging-of-the-interaction-of-amyloid-beta-40-peptides-with-live-cells-and-model-membrane
#19
Elaheh Jamasbi, Mohammed Akhter Hossain, Marsha Tan, Frances Separovic, Giuseppe D Ciccotosto
Amyloid beta peptides (Aβ) found in plaques in the brain have been widely recognised as a hallmark of Alzheimer's disease although the underlying mechanism is still unknown. Aβ40 and Aβ40(A2T) peptides were synthesized and their effects on neuronal cells are reported together with the effect of tetramer forms of the peptides. ThT assay revealed that mutation affected the lag time and aggregation and the presence of lipid vesicles changed the fibril formation profile for both peptides. The A2T mutation appeared to reduce cytotoxicity and lessen binding of Aβ40 peptides to neuronal cells...
February 7, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29386468/simulation-study-on-complex-conformations-of-a%C3%AE-42-peptides-on-a-gm1-ganglioside-containing-lipid-membrane
#20
Majid Vahed, Saburo Neya, Katsumi Matsuzaki, Tyuji Hoshino
Aggregation and complex formation of amyloid beta (Aβ) peptides on a neuronal cell membrane is a hallmark of neuro-disturbance diseases. In this work, we performed molecular dynamics (MD) simulations to investigate the initial stage of interactions of multiple Aβ42 peptides on a GM1 ganglioside-containing membrane that mimics a micro-domain on the neuronal cell surface. Conformational changes of Aβs due to adhesion on the membrane and subsequent molecular interactions among the Aβs were monitored. It was suggested from results of the two 1...
2018: Chemical & Pharmaceutical Bulletin
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