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Lithium ions display weak interaction with amyloid-beta (Aβ) peptides and have minor effects on their aggregation
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik. Tallinn University of Technology, Estonia.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
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Antal upphovsmän: 92021 (Engelska)Ingår i: Acta Biochimica Polonica, ISSN 0001-527X, E-ISSN 1734-154X, Vol. 68, nr 2, s. 169-179Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Alzheimer’s disease (AD) is an incurable disease and the main cause of age-related dementia worldwide, despite decades of research. Treatment of AD with lithium (Li) has shown promising results, but the underlying mechanism is unclear. The pathological hallmark of AD brains is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils. The plaques contain also metal ions of e.g. Cu, Fe, and Zn, and such ions are known to interact with Aβ peptides and modulate their aggregation and toxicity. The interactions between Aβ peptides and Li+ions have however not been well investigated. Here, we use a range of biophysical techniques to characterize in vitro interactions between Aβ peptides and Li+ions. We show that Li+ions display weak and non-specific interactions with Aβ peptides, and have minor effects on Aβ aggregation. These results indicate that possible beneficial effects of Li on AD pathology are not likely caused by direct interactions between Aβ peptides and Li+ions.

Ort, förlag, år, upplaga, sidor
2021. Vol. 68, nr 2, s. 169-179
Nyckelord [en]
Alzheimer's disease, protein aggregation, metal-protein binding, neurodegeneration, pharmaceutics
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
URN: urn:nbn:se:su:diva-196438DOI: 10.18388/abp.2020_5493ISI: 000659435200003PubMedID: 33909969OAI: oai:DiVA.org:su-196438DiVA, id: diva2:1592116
Tillgänglig från: 2021-09-08 Skapad: 2021-09-08 Senast uppdaterad: 2022-10-11Bibliografiskt granskad
Ingår i avhandling
1. Structure and dynamics of amyloid-beta oligomers
Öppna denna publikation i ny flik eller fönster >>Structure and dynamics of amyloid-beta oligomers
2022 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Alzheimer's disease (AD) is the most common cause of dementia, affects tens of millions of people all over the world and inflicts huge socioeconomic costs on the societies. AD is a neurodegenerative disease; it progresses over time and is highly debilitating at the advanced stages. Biochemical and genetic studies in the last decades have revealed that amyloid-beta (Aβ) peptides play underlying roles in the molecular pathology of AD. Aβ peptides are small, aggregation-prone polypeptides produced in the neural tissue. Soluble aggregates of Aβ peptides, known as Aβ oligomers are regarded as the major neurotoxic species in AD brain.

In this thesis, in vitro studies were performed on Aβ oligomers with a number of spectroscopy and biochemical methods. The main technique used in this thesis is infrared (IR) spectroscopy, a variety of vibrational spectroscopy methods. IR spectroscopy measures the absorption of IR radiation by the vibrational transitions of oscillating dipoles within chemical structures and provides structural information on chemical bonds and functional groups in molecules. The method can provide valuable data on the secondary structure of proteins and therefore is a powerful tool for studying protein self-assembly and aggregation.

Different samples of homogeneous and heterogeneous Aβ42 oligomers were prepared and studied with IR spectroscopy and biochemical methods to establish correlations between oligomers' physical properties (size and homogeneity) and IR parameters. Additionally, the effects of lithium and nickel ions on the formation of homogeneous Aβ42 oligomers were studied. Separately, isotope-edited IR spectroscopy was used to study the molecular structure of homogeneous and heterogeneous Aβ42 oligomers. The obtained data can be helpful to establish IR spectroscopy for characterization of Aβ oligomers, as well as studies on their dynamics and interactions with each other and other biomolecules or inorganic materials. Moreover, the findings in this thesis add to the available knowledge on the molecular structure of Aβ oligomers and help to develop relevant molecular models. Such information can be helpful for the development of diagnostics and therapeutic strategies for AD.

Ort, förlag, år, upplaga, sidor
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2022. s. 97
Nyckelord
Alzheimer's disease, amyloid-beta peptide, Aβ oligomer, infrared spectroscopy, FTIR, protein aggregation, β-sheet, interaction, lithium, nickel
Nationell ämneskategori
Biokemi och molekylärbiologi Strukturbiologi Neurovetenskaper
Forskningsämne
biokemi
Identifikatorer
urn:nbn:se:su:diva-210305 (URN)978-91-8014-052-2 (ISBN)978-91-8014-053-9 (ISBN)
Disputation
2022-11-25, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16B and online via Zoom: https://stockholmuniversity.zoom.us/j/4563593316, Stockholm, 14:00 (Engelska)
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Handledare
Tillgänglig från: 2022-11-01 Skapad: 2022-10-11 Senast uppdaterad: 2022-11-01Bibliografiskt granskad

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Berntsson, ElinaPaul, SumanVosough, FarazJarvet, JüriBarth, AndreasGräslund, AstridWärmländer, Sebastian

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Berntsson, ElinaPaul, SumanVosough, FarazJarvet, JüriBarth, AndreasGräslund, AstridWärmländer, Sebastian
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Institutionen för biokemi och biofysik
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Acta Biochimica Polonica
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