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Synuclein electrochemical

Shaopei Li, Kagan Kerman
Herein we present a proof of concept study for electrochemical detection of the metal-binding site of α-synuclein (α-syn). Parkinson's disease (PD) is associated with the aggregation and misfolding of α-syn in dopaminergic neurons. Since copper homeostasis is deregulated in PD, it is of great significance to study the metal-binding site of wild-type (WT) α-syn (48-53, VVHGVA), and its pathological mutants (H50Q, and G51D). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to monitor the formation of peptide-PEG mixed layer on gold surfaces...
February 19, 2019: Analytical Chemistry
Münteha Nur Sonuç Karaboğa, Mustafa Kemal Sezgintürk
Alpha-synuclein (SYN) is a prominent key protein in Parkinson-type dementia. Measurement of the amount of this protein found in the cerebrospinal fluid (CSF) using precise techniques may help in the diagnosis and prognosis of the disease. In this study, a gold nanoparticle (AuNP)-polyglutamic acid (PGA)-modified indium tin oxide (ITO)-based disposable neuro-biosensor system was designed for alpha-synuclein (alpha-SYN), an important biomarker of Parkinson's disease. Glutamic acid was formed by electropolymerization on the electrode surface...
November 20, 2018: Analyst
Seyed Mohammad Taghdisi, Noor Mohammad Danesh, Morteza Alinezhad Nameghi, Mohammad Ramezani, Mona Alibolandi, Mohammad Hassanzadeh-Khayat, Ahmad Sarreshtehdar Emrani, Khalil Abnous
This study describes a novel electrochemical aptasensor for detection of α-synuclein (α-syn) oligomer, an important biomarker related to Parkinson's and Alzheimer's diseases. The sensing platform is based on exonuclease I (Exo I), terminal deoxynucleotidyl transferase (TdT) and methylene blue. The aptasensor exploits the improved sensitivity because of applications of TdT and Exo I and also a label-free aptamer (Apt). Furthermore, direct immobilization of complementary strand of aptamer (CS) instead of Apt on the surface of electrode prohibits Apt self-assembled monolayer aggregation and keeps the function of the Apt...
September 25, 2018: Biosensors & Bioelectronics
Ori J Lieberman, Se Joon Choi, Ellen Kanter, Anastasia Saverchenko, Micah D Frier, Giulia M Fiore, Min Wu, Jyothisri Kondapalli, Enrico Zampese, D James Surmeier, David Sulzer, Eugene V Mosharov
Parkinson's disease (PD) is a debilitating neurodegenerative disease characterized by a loss of dopaminergic neurons in the substantia nigra (SN). Although mitochondrial dysfunction and dysregulated α-synuclein (aSyn) expression are postulated to play a role in PD pathogenesis, it is still debated why neurons of the SN are targeted while neighboring dopaminergic neurons of the ventral tegmental area (VTA) are spared. Using electrochemical and imaging approaches, we investigated metabolic changes in cultured primary mouse midbrain dopaminergic neurons exposed to a parkinsonian neurotoxin, 1-methyl-4-phenylpyridinium (MPP+ )...
November 2017: ENeuro
Niels Kruse, Omar M El-Agnaf, Brit Mollenhauer
AIM: α-Synuclein (aSyn), a putative cerebrospinal fluid biomarker, may support the diagnosis of neurodegenerative diseases. Previous studies led to conflicting results due to different preanalytical and analytical procedures. Standardized assays are required to allow for comparison of results from different laboratories. MATERIALS & METHODS: We performed a side-by-side validation of a commercially available (MSD, MD, USA) and a 'homebrew' assay for quantification of aSyn according to published guidelines...
April 2017: Bioanalysis
Kai-Chih Hung, Hui-Ju Huang, Yi-Ting Wang, Anya Maan-Yuh Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Neuroinflammation, oxidative stress, and protein aggregation form a vicious cycle in the pathophysiology of Parkinson's disease (PD); activated microglia is the main location of neuroinflammation. A Chinese medicine book, "Shanghan Lun", known as the "Treatises on Cold damage Diseases" has suggested that Scutellaria baicalensis Georgi is effective in treating CNS diseases. The anti-inflammatory mechanisms of baicalein, a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi, remain to be explored...
December 24, 2016: Journal of Ethnopharmacology
Xin R Cheng, Gregory Q Wallace, François Lagugné-Labarthet, Kagan Kerman
In this proof-of-concept study, the fabrication of novel Au nanostructured indium tin oxide (Au-ITO) surfaces is described for the development of a dual-detection platform with electrochemical and localized surface plasmon resonance (LSPR)-based biosensing capabilities. Nanosphere lithography (NSL) was applied to fabricate Au-ITO surfaces. Oligomers of α-synuclein (αS) were covalently immobilized to determine the electrochemical and LSPR characteristics of the protein. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were performed using the redox probe [Fe(CN)6](3-/4-) to detect the binding of Cu(II) ions and (-)-epigallocatechin-3-gallate (EGCG) to αS on the Au-ITO surface...
February 25, 2015: ACS Applied Materials & Interfaces
Qiao Xu, Ho Cheng, Joshua Lehr, Amol V Patil, Jason J Davis
A reliable quantification of protein markers will undoubtedly underpin profound developments in disease surveillance, diagnostics, and improved therapy. Although there potentially exist numerous means of achieving this, electrochemical impedimetric techniques offer scale of sensitivity, cost, convenience, and a flexibility with which few alternatives can compete. Though there have been marked developments in electroanalytical protein detection, the demands associated with accessing the inherent assay sensitivity in complex biological media largely remains...
January 6, 2015: Analytical Chemistry
Marina A Gruden, Tatiana V Davydova, Victor B Narkevich, Valentina G Fomina, Chao Wang, Vladimir S Kudrin, Ludmilla A Morozova-Roche, Robert D E Sewell
Alpha-synuclein (α-syn) toxic aggregates delivered by the nasal vector have been shown to modify the neurochemistry of dopamine (DA) which is associated with parkinsonian-like motor symptoms. The aim was therefore to study the intranasal effects of α-syn oligomers, fibrils or their combination on the motor behavior of aged mice in relation to possible noradrenergic and serotonergic correlates. In vitro generated α-syn oligomers and fibrils were verified using atomic force microscopy and the thioflavin T binding assay...
February 15, 2015: Behavioural Brain Research
M Bartošík, E Paleček, B Vojtěšek
Electrochemical analysis of nucleic acids, proteins and polysaccharides represents an interesting, although not widely spread alternative to current methods based predominantly on optical detection because it offers a relatively inexpensive, fast and instrumentally simple detection of parallel samples on miniaturized chips, ideal for personalized medicine of the 21st century. Nucleic acid electrochemistry enables, for example, detection of specific DNA sequences (for determination of genes or presence of bacteria and viruses, etc...
2014: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Paula Lopes, Hans Dyrnesli, Nikolai Lorenzen, Daniel Otzen, Elena E Ferapontova
Amyloid formation of proteins and peptides is an important biomedical and biotechnological problem, intensively studied and yet not fully understood. In this context, the development of fast and reliable methods for real-time monitoring of protein misfolding is of particular importance for unambiguous establishment of disease-, drug- and environmentally induced mechanisms of protein aggregation. Here we show that the extent of aggregation of α-synuclein (αSN), involved in Parkinson's disease and other neurodegenerative disorders, can be electrochemically monitored by oxidizing tyrosine (Tyr) residues surface-exposed in monomeric αSN and buried in fibrillated αSN adsorbed onto graphite electrodes...
February 21, 2014: Analyst
Agata Ziomber, Piotr Thor, Anna Krygowska-Wajs, Tomasz Załęcki, Marek Moskała, Irena Romańska, Jerzy Michaluk, Lucyna Antkiewicz-Michaluk
BACKGROUND: Recent clinical studies have shown that the dorsal motor nucleus of the vagus nerve is one of the brain areas that are the earliest affected by α-synuclein and Lewy body pathology in Parkinson's disease. This observation raises the question: how the vagus nerve dysfunction affects the dopamine system in the brain? METHODS: The rats underwent surgical implantation of the microchip (MC) in the abdominal region of the vagus. In this study, we examined the effect of chronic, unilateral electrical stimulation of the left nerve vagus, of two different types: low-frequency (MCL) and physiological stimulation (MCPh) on the dopamine and serotonin metabolism determined by high-pressure chromatography with electrochemical detection in rat brain structures...
2012: Pharmacological Reports: PR
Binbin Zhou, Yuanqiang Hao, Chengshan Wang, Ding Li, You-Nian Liu, Feimeng Zhou
The intracellular α-synuclein (α-syn) protein, whose conformational change and aggregation have been closely linked to the pathology of Parkingson's disease (PD), is highly populated at the presynaptic termini and remains there in the α-helical conformation. In this study, circular dichroism confirmed that natively unstructured α-syn in aqueous solution was transformed to its α-helical conformation upon addition of trifluoroethanol (TFE). Electrochemical and UV-visible spectroscopic experiments reveal that both Cu (I) and Cu (II) are stabilized, with the former being stabilized by about two orders of magnitude...
January 2013: Journal of Inorganic Biochemistry
Tiffiny Chan, Ari M Chow, Xin R Cheng, Derek W F Tang, Ian R Brown, Kagan Kerman
The interaction of dopamine (DA) and α-synuclein (α-S) can lead to protein misfolding and neuronal death triggered by oxidative stress relevant to the progression of Parkinson's disease (PD). In this study, interfacial properties associated with DA-induced α-S aggregation under various solution conditions (i.e., pH, ionic strength) were investigated in vitro. The electrochemical oxidation of tyrosine (Tyr) residues in α-S was detected in the presence of DA. DA concentration dependence was analyzed and found to significantly affect α-S aggregation pathways...
July 18, 2012: ACS Chemical Neuroscience
Claudio D Borsarelli, Lisandro J Falomir-Lockhart, Veronika Ostatná, Jonathan A Fauerbach, He-Hsuan Hsiao, Henning Urlaub, Emil Paleček, Elizabeth A Jares-Erijman, Thomas M Jovin
Alpha-synuclein (αS), a 140 amino acid presynaptic protein, is the major component of the fibrillar aggregates (Lewy bodies) observed in dopaminergic neurons of patients affected by Parkinson's disease. It is currently believed that noncovalent oligomeric forms of αS, arising as intermediates in its aggregation, may constitute the major neurotoxic species. However, attempts to isolate and characterize such oligomers in vitro, and even more so in living cells, have been hampered by their transient nature, low concentration, polymorphism, and inherent instability...
August 15, 2012: Free Radical Biology & Medicine
Veronika Ostatná, Hana Cernocká, Katarzyna Kurzątkowska, Emil Paleček
In an attempt to develop a label-free electrochemical method for detection of changes in protein structures based on oxidizability of tyrosine and tryptophan residues we tested different types of carbon electrodes. We found that using edge plane pyrolytic graphite electrode (EPGE) we can discriminate between native and denatured forms of human serum albumin (HSA) and of other proteins, such as bovine and chicken serum albumin, aldolase and concanavalin. Treatment of natively unfolded α-synuclein with 8 M urea resulted only in a small change in the tyrosine oxidation peak, in a good agreement with absence of highly ordered structure in this protein...
July 20, 2012: Analytica Chimica Acta
Yarui An, Xiaoli Jiang, Wenji Bi, Hua Chen, Litong Jin, Shengping Zhang, Chuangui Wang, Wen Zhang
A novel electrochemical immunosensor for sensitive detection of α-synuclein (α-SYN), a very important neuronal protein, has been developed based on dual signal amplification strategy. Herein, G4-polyamidoamine dendrimer-encapsulated Au nanoparticles (PAMAM-Au nanocomposites) were covalently bound on the poly-o-aminobenzoic acid (poly-o-ABA), which was initially electropolymerized on the electrode surface to perform abundant carboxyl groups. The formed immunosensor platform, PAMAM-Au, was proved to provide numerous amino groups to allow highly dense immobilization of antigen, and facilitate the improvement of electrochemical responses as well...
February 15, 2012: Biosensors & Bioelectronics
Sabina Anwar, Owen Peters, Steven Millership, Natalia Ninkina, Natalie Doig, Natalie Connor-Robson, Sarah Threlfell, Gurdeep Kooner, Robert M Deacon, David M Bannerman, J Paul Bolam, Sreeganga S Chandra, Stephanie J Cragg, Richard Wade-Martins, Vladimir L Buchman
The synucleins (α, β, and γ) are highly homologous proteins thought to play a role in regulating neurotransmission and are found abundantly in presynaptic terminals. To overcome functional overlap between synuclein proteins and to understand their role in presynaptic signaling from mesostriatal dopaminergic neurons, we produced mice lacking all three members of the synuclein family. The effect on the mesostriatal system was assessed in adult (4- to 14-month-old) animals using a combination of behavioral, biochemical, histological, and electrochemical techniques...
May 18, 2011: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yarui An, Linlin Tang, Xiaoli Jiang, Hua Chen, Meicheng Yang, Litong Jin, Shengping Zhang, Chuangui Wang, Wen Zhang
α-Synuclein (α-SYN) is a very important neuronal protein that is associated with Parkinson's disease. In this paper, we utilized Au-doped TiO(2) nanotube arrays to design a photoelectrochemical immunosensor for the detection of α-SYN. The highly ordered TiO(2) nanotubes were fabricated by using an electrochemical anodization technique on pure Ti foil. After that, a photoelectrochemical deposition method was exploited to modify the resulting nanotubes with Au nanoparticles, which have been demonstrated to facilitate the improvement of photocurrent responses...
December 27, 2010: Chemistry: a European Journal
Yong Peng, Chengshan Wang, Howard H Xu, You-Nian Liu, Feimeng Zhou
Parkinson's disease (PD) is hallmarked by the abnormal intracellular inclusions (Lewy bodies or LBs) in dopaminergic cells. Amyloidogenic protein alpha-synuclein (alpha-syn) and iron (including both Fe(III) and Fe(II)) are both found to be present in LBs. The interaction between iron and alpha-syn might have important biological relevance to PD etiology. Previously, a moderate binding affinity between alpha-syn and Fe(II) (5.8x10(3)M(-1)) has been measured, but studies on the binding between alpha-syn and Fe(III) have not been reported...
April 2010: Journal of Inorganic Biochemistry
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