Endre søk
Link to record
Permanent link

Direct link
Publikasjoner (7 av 7) Visa alla publikasjoner
Paul, S., Jenistova, A., Vosough, F., Berntsson, E., Mörman, C., Jarvet, J., . . . Barth, A. (2023). 13C- and 15N-labeling of amyloid-β and inhibitory peptides to study their interaction via nanoscale infrared spectroscopy. Communications Chemistry, 6(1), Article ID 163.
Åpne denne publikasjonen i ny fane eller vindu >>13C- and 15N-labeling of amyloid-β and inhibitory peptides to study their interaction via nanoscale infrared spectroscopy
Vise andre…
2023 (engelsk)Inngår i: Communications Chemistry, E-ISSN 2399-3669, Vol. 6, nr 1, artikkel-id 163Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Interactions between molecules are fundamental in biology. They occur also between amyloidogenic peptides or proteins that are associated with different amyloid diseases, which makes it important to study the mutual influence of two polypeptides on each other's properties in mixed samples. However, addressing this research question with imaging techniques faces the challenge to distinguish different polypeptides without adding artificial probes for detection. Here, we show that nanoscale infrared spectroscopy in combination with C-13, N-15-labeling solves this problem. We studied aggregated amyloid-& beta; peptide (A & beta;) and its interaction with an inhibitory peptide (NCAM1-PrP) using scattering-type scanning near-field optical microscopy. Although having similar secondary structure, labeled and unlabeled peptides could be distinguished by comparing optical phase images taken at wavenumbers characteristic for either the labeled or the unlabeled peptide. NCAM1-PrP seems to be able to associate with or to dissolve existing A & beta; fibrils because pure A & beta; fibrils were not detected after mixing. Interactions of proteins or polypeptides with different secondary structures can be studied in a mixture by nanoscale infrared spectroscopy, however, this technique remains challenging for polypeptides with similar secondary structures. Here, the authors demonstrate clear discrimination of two polypeptides from a mixture by scattering-type scanning near-field optical microscopy when one of the components is labeled with C-13- and N-15-isotopes.

HSV kategori
Identifikatorer
urn:nbn:se:su:diva-221129 (URN)10.1038/s42004-023-00955-w (DOI)001042052900001 ()37537303 (PubMedID)2-s2.0-85167397298 (Scopus ID)
Tilgjengelig fra: 2023-09-18 Laget: 2023-09-18 Sist oppdatert: 2023-09-18bibliografisk kontrollert
Berntsson, E., Vosough, F., Noormagi, A., Padari, K., Asplund, F., Gielnik, M., . . . Wärmländer, S. (2023). Characterization of Uranyl (UO22+) Ion Binding to Amyloid Beta (Aβ) Peptides: Effects on Aβ Structure and Aggregation. ACS Chemical Neuroscience, 14(15), 2618-2633
Åpne denne publikasjonen i ny fane eller vindu >>Characterization of Uranyl (UO22+) Ion Binding to Amyloid Beta (Aβ) Peptides: Effects on Aβ Structure and Aggregation
Vise andre…
2023 (engelsk)Inngår i: ACS Chemical Neuroscience, E-ISSN 1948-7193, Vol. 14, nr 15, s. 2618-2633Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Uranium (U) is naturally present in ambient air, water, and soil, and depleted uranium (DU) is released into the environment via industrial and military activities. While the radiological damage from U is rather well understood, less is known about the chemical damage mechanisms, which dominate in DU. Heavy metal exposure is associated with numerous health conditions, including Alzheimer’s disease (AD), the most prevalent age-related cause of dementia. The pathological hallmark of AD is the deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils in the brain. However, the toxic species in AD are likely oligomeric Aβ aggregates. Exposure to heavy metals such as Cd, Hg, Mn, and Pb is known to increase Aβ production, and these metals bind to Aβ peptides and modulate their aggregation. The possible effects of U in AD pathology have been sparsely studied. Here, we use biophysical techniques to study in vitro interactions between Aβ peptides and uranyl ions, UO22+, of DU. We show for the first time that uranyl ions bind to Aβ peptides with affinities in the micromolar range, induce structural changes in Aβ monomers and oligomers, and inhibit Aβ fibrillization. This suggests a possible link between AD and U exposure, which could be further explored by cell, animal, and epidemiological studies. General toxic mechanisms of uranyl ions could be modulation of protein folding, misfolding, and aggregation. 

Emneord
Alzheimer's disease, amyloid aggregation, metal-protein binding, neurodegeneration, heavy metal toxicity
HSV kategori
Identifikatorer
urn:nbn:se:su:diva-221233 (URN)10.1021/acschemneuro.3c00130 (DOI)001035034000001 ()37487115 (PubMedID)2-s2.0-85166386170 (Scopus ID)
Tilgjengelig fra: 2023-09-19 Laget: 2023-09-19 Sist oppdatert: 2023-09-19bibliografisk kontrollert
Berntsson, E., Vosough, F., Svantesson, T., Pansieri, J., Iashchishyn, I. A., Ostojic, L., . . . Wärmländer, S. (2023). Residue-specific binding of Ni(II) ions influences the structure and aggregation of amyloid beta (Aβ) peptides. Scientific Reports, 13(1), Article ID 3341.
Åpne denne publikasjonen i ny fane eller vindu >>Residue-specific binding of Ni(II) ions influences the structure and aggregation of amyloid beta (Aβ) peptides
Vise andre…
2023 (engelsk)Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 13, nr 1, artikkel-id 3341Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Alzheimer's disease (AD) is the most common cause of dementia worldwide. AD brains display deposits of insoluble amyloid plaques consisting mainly of aggregated amyloid-beta (A beta) peptides, and A beta oligomers are likely a toxic species in AD pathology. AD patients display altered metal homeostasis, and AD plaques show elevated concentrations of metals such as Cu, Fe, and Zn. Yet, the metal chemistry in AD pathology remains unclear. Ni(II) ions are known to interact with A beta peptides, but the nature and effects of such interactions are unknown. Here, we use numerous biophysical methods-mainly spectroscopy and imaging techniques-to characterize A beta/Ni(II) interactions in vitro, for different A beta variants: A beta(1-40), A beta(1-40)(H6A, H13A, H14A), A beta(4-40), and A beta(1-42). We show for the first time that Ni(II) ions display specific binding to the N-terminal segment of full-length A beta monomers. Equimolar amounts of Ni(II) ions retard A beta aggregation and direct it towards non-structured aggregates. The His6, His13, and His14 residues are implicated as binding ligands, and the Ni(II)center dot A beta binding affinity is in the low mu M range. The redox-active Ni(II) ions induce formation of dityrosine cross-links via redox chemistry, thereby creating covalent A beta dimers. In aqueous buffer Ni(II) ions promote formation of beta sheet structure in A beta monomers, while in a membrane-mimicking environment (SDS micelles) coil-coil helix interactions appear to be induced. For SDS-stabilized A beta oligomers, Ni(II) ions direct the oligomers towards larger sizes and more diverse (heterogeneous) populations. All of these structural rearrangements may be relevant for the A beta aggregation processes that are involved in AD brain pathology.

HSV kategori
Identifikatorer
urn:nbn:se:su:diva-229707 (URN)10.1038/s41598-023-29901-5 (DOI)000986236800026 ()36849796 (PubMedID)
Tilgjengelig fra: 2024-05-29 Laget: 2024-05-29 Sist oppdatert: 2024-05-29bibliografisk kontrollert
Vosough, F. (2022). Structure and dynamics of amyloid-beta oligomers. (Doctoral dissertation). Stockholm: Department of Biochemistry and Biophysics, Stockholm University
Åpne denne publikasjonen i ny fane eller vindu >>Structure and dynamics of amyloid-beta oligomers
2022 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2022. s. 97
Emneord
Alzheimer's disease, amyloid-beta peptide, Aβ oligomer, infrared spectroscopy, FTIR, protein aggregation, β-sheet, interaction, lithium, nickel
HSV kategori
Forskningsprogram
biokemi
Identifikatorer
urn:nbn:se:su:diva-210305 (URN)978-91-8014-052-2 (ISBN)978-91-8014-053-9 (ISBN)
Disputas
2022-11-25, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16B and online via Zoom: https://stockholmuniversity.zoom.us/j/4563593316, Stockholm, 14:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2022-11-01 Laget: 2022-10-11 Sist oppdatert: 2022-11-01bibliografisk kontrollert
Vosough, F. & Barth, A. (2021). Characterization of Homogeneous and Heterogeneous Amyloid-beta 42 Oligomer Preparations with Biochemical Methods and Infrared Spectroscopy Reveals a Correlation between Infrared Spectrum and Oligomer Size. ACS Chemical Neuroscience, 12(3), 473-488
Åpne denne publikasjonen i ny fane eller vindu >>Characterization of Homogeneous and Heterogeneous Amyloid-beta 42 Oligomer Preparations with Biochemical Methods and Infrared Spectroscopy Reveals a Correlation between Infrared Spectrum and Oligomer Size
2021 (engelsk)Inngår i: ACS Chemical Neuroscience, E-ISSN 1948-7193, Vol. 12, nr 3, s. 473-488Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Soluble oligomers of the amyloid-β(1-42) (Aβ42) peptide, widely considered to be among the relevant neurotoxic species involved in Alzheimer’s disease, were characterized with a combination of biochemical and biophysical methods. Homogeneous and stable Aβ42 oligomers were prepared by treating monomeric solutions of the peptide with detergents. The prepared oligomeric solutions were analyzed with blue native and sodium dodecyl sulfate polyacrylamide gel electrophoresis, as well as with infrared (IR) spectroscopy. The IR spectra indicated a well-defined β-sheet structure of the prepared oligomers. We also found a relationship between the size/molecular weight of the Aβ42 oligomers and their IR spectra: The position of the main amide I′ band of the peptide backbone correlated with oligomer size, with larger oligomers being associated with lower wavenumbers. This relationship explained the time-dependent band shift observed in time-resolved IR studies of Aβ42 aggregation in the absence of detergents, during which the oligomer size increased. In addition, the bandwidth of the main IR band in the amide I′ region was found to become narrower with time in our time-resolved aggregation experiments, indicating a more homogeneous absorption of the β-sheets of the oligomers after several hours of aggregation. This is predominantly due to the consumption of smaller oligomers in the aggregation process.

Emneord
Amyloid-beta peptide, antiparallel beta-sheet, FTIR spectroscopy, infrared spectroscopy, oligomer
HSV kategori
Identifikatorer
urn:nbn:se:su:diva-191785 (URN)10.1021/acschemneuro.0c00642 (DOI)000618157100010 ()33455165 (PubMedID)
Tilgjengelig fra: 2021-04-27 Laget: 2021-04-27 Sist oppdatert: 2023-08-28bibliografisk kontrollert
Berntsson, E., Paul, S., Vosough, F., Sholts, S. B., Jarvet, J., Roos, P. M., . . . Wärmländer, S. (2021). Lithium ions display weak interaction with amyloid-beta (Aβ) peptides and have minor effects on their aggregation. Acta Biochimica Polonica, 68(2), 169-179
Åpne denne publikasjonen i ny fane eller vindu >>Lithium ions display weak interaction with amyloid-beta (Aβ) peptides and have minor effects on their aggregation
Vise andre…
2021 (engelsk)Inngår i: Acta Biochimica Polonica, ISSN 0001-527X, E-ISSN 1734-154X, Vol. 68, nr 2, s. 169-179Artikkel i tidsskrift (Fagfellevurdert) 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.

Emneord
Alzheimer's disease, protein aggregation, metal-protein binding, neurodegeneration, pharmaceutics
HSV kategori
Identifikatorer
urn:nbn:se:su:diva-196438 (URN)10.18388/abp.2020_5493 (DOI)000659435200003 ()33909969 (PubMedID)
Tilgjengelig fra: 2021-09-08 Laget: 2021-09-08 Sist oppdatert: 2022-10-11bibliografisk kontrollert
Król, S., Österlund, N., Vosough, F., Jarvet, J., Wärmländer, S., Barth, A., . . . Mörman, C. (2021). The amyloid-inhibiting NCAM-PrP peptide targets Aβ peptide aggregation in membrane-mimetic environments. iScience, 24(8), Article ID 102852.
Åpne denne publikasjonen i ny fane eller vindu >>The amyloid-inhibiting NCAM-PrP peptide targets Aβ peptide aggregation in membrane-mimetic environments
Vise andre…
2021 (engelsk)Inngår i: iScience, E-ISSN 2589-0042 , Vol. 24, nr 8, artikkel-id 102852Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Substantial research efforts have gone into elucidating the role of protein misfolding and self-assembly in the onset and progression of Alzheimer’s disease (AD). Aggregation of the Amyloid-β (Aβ) peptide into insoluble fibrils is closely associated with AD. Here, we use biophysical techniques to study a peptide-based approach to target Aβ amyloid aggregation. A peptide construct, NCAM-PrP, consists of a largely hydrophobic signal sequence linked to a positively charged hexapeptide. The NCAM-PrP peptide inhibits Aβ amyloid formation by forming aggregates which are unavailable for further amyloid aggregation. In a membrane-mimetic environment, Aβ and NCAM-PrP form specific heterooligomeric complexes, which are of lower aggregation states compared to Aβ homooligomers. The Aβ:NCAM-PrP interaction appears to take place on different aggregation states depending on the absence or presence of a membrane-mimicking environment. These insights can be useful for the development of potential future therapeutic strategies targeting Aβ at several aggregation states.

HSV kategori
Identifikatorer
urn:nbn:se:su:diva-198433 (URN)10.1016/j.isci.2021.102852 (DOI)000686897200039 ()34381976 (PubMedID)
Tilgjengelig fra: 2021-11-09 Laget: 2021-11-09 Sist oppdatert: 2023-09-04bibliografisk kontrollert
Organisasjoner
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0001-5856-3226