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Publikationer (8 of 8) Visa alla publikationer
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.
Öppna denna publikation i ny flik eller fönster >>13C- and 15N-labeling of amyloid-β and inhibitory peptides to study their interaction via nanoscale infrared spectroscopy
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2023 (Engelska)Ingår i: Communications Chemistry, E-ISSN 2399-3669, Vol. 6, nr 1, artikel-id 163Artikel i tidskrift (Refereegranskat) 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.

Nationell ämneskategori
Kemi Biokemi och molekylärbiologi
Identifikatorer
urn:nbn:se:su:diva-221129 (URN)10.1038/s42004-023-00955-w (DOI)001042052900001 ()37537303 (PubMedID)2-s2.0-85167397298 (Scopus ID)
Tillgänglig från: 2023-09-18 Skapad: 2023-09-18 Senast uppdaterad: 2023-09-18Bibliografiskt granskad
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
Öppna denna publikation i ny flik eller fönster >>Characterization of Uranyl (UO22+) Ion Binding to Amyloid Beta (Aβ) Peptides: Effects on Aβ Structure and Aggregation
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2023 (Engelska)Ingår i: ACS Chemical Neuroscience, E-ISSN 1948-7193, Vol. 14, nr 15, s. 2618-2633Artikel i tidskrift (Refereegranskat) 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. 

Nyckelord
Alzheimer's disease, amyloid aggregation, metal-protein binding, neurodegeneration, heavy metal toxicity
Nationell ämneskategori
Neurovetenskaper Biokemi och molekylärbiologi
Identifikatorer
urn:nbn:se:su:diva-221233 (URN)10.1021/acschemneuro.3c00130 (DOI)001035034000001 ()37487115 (PubMedID)2-s2.0-85166386170 (Scopus ID)
Tillgänglig från: 2023-09-19 Skapad: 2023-09-19 Senast uppdaterad: 2023-09-19Bibliografiskt granskad
Noormägi, A., Golubeva, T., Berntsson, E., Wärmländer, S. K. T., Tõugu, V. & Palumaa, P. (2023). Direct Competition of ATCUN Peptides with Human Serum Albumin for Copper(II) Ions Determined by LC-ICP MS. ACS Omega, 8(37), 33912-33919
Öppna denna publikation i ny flik eller fönster >>Direct Competition of ATCUN Peptides with Human Serum Albumin for Copper(II) Ions Determined by LC-ICP MS
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2023 (Engelska)Ingår i: ACS Omega, E-ISSN 2470-1343, Vol. 8, nr 37, s. 33912-33919Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Copper is an indispensable biometal, primarily serving as a redox-competent cofactor in numerous proteins. Apart from preformed copper-binding sites within the protein structures, small peptide motifs exist called ATCUN, which are composed of an N-terminal tripeptide XZH, able to bind Cu(II) ions in exchangeable form. These motifs are common for serum albumin, but they are also present in a wide range of proteins and peptides. These proteins and peptides can be involved in copper metabolism, and copper ions can affect their biological role. The distribution of copper between the ATCUN peptides, including truncated amyloid-β (Aβ) peptides Aβ4–42 and Aβ11–42, which may be involved in Alzheimer’s disease pathogenesis, is mainly determined by their concentrations and relative Cu(II)-binding affinities. The Cu(II)-binding affinity (log Kd) of several ATCUN peptides, determined by different methods and authors, varies by more than three orders of magnitude. This variation may be attributed to the chemical properties of peptides but can also be influenced by the differences in methods and experimental conditions used for the determination of Kd. In the current study, we performed direct competition experiments between selected ATCUN peptides and HSA by using an LC-ICP MS-based approach. We demonstrated that ATCUN and truncated Aβ peptides Aβ4–16 and Aβ11–15 bind Cu(II) ions with an affinity similar to that for HSA. Our results demonstrate that ATCUN motifs cannot compete with excess HSA for the binding of Cu(II) ions in the blood and cerebrospinal fluid. 

Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
urn:nbn:se:su:diva-223038 (URN)10.1021/acsomega.3c04649 (DOI)001070106300001 ()2-s2.0-85173171732 (Scopus ID)
Tillgänglig från: 2023-10-18 Skapad: 2023-10-18 Senast uppdaterad: 2024-03-26Bibliografiskt granskad
Koski, L., Berntsson, E., Vikström, M., Wärmländer, S. K. T. & Roos, P. M. (2023). Metal ratios as possible biomarkers for amyotrophic lateral sclerosis. Journal of Trace Elements in Medicine and Biology, 78, Article ID 127163.
Öppna denna publikation i ny flik eller fönster >>Metal ratios as possible biomarkers for amyotrophic lateral sclerosis
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2023 (Engelska)Ingår i: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 78, artikel-id 127163Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown aetiology. Metals have been suspected to contribute to ALS pathogenesis since mid-19th century, yet studies on measured metal concentrations in ALS patients have often yielded conflicting results, with large individual variation in measured values. Calculating metal concentration ratios can unveil possible synergistic effects of neurotoxic metals in ALS pathogenesis. The aim of this study was to investigate if ratios of different metal concentrations in cerebrospinal fluid (CSF) and blood plasma, respectively, differ between ALS patients and healthy controls.

Methods: Cerebrospinal fluid and blood plasma were collected from 17 ALS patients and 10 controls. Samples were analysed for 22 metals by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS), and all possible 231 metal ratios calculated in each body fluid.

Results: Fifty-three metal ratios were significantly elevated in ALS cases as compared to controls (p < 0.05); five in blood plasma, and 48 in CSF. The finding of fewer elevated ratios in blood plasma may indicate specific transport of metals into the central nervous system. The elevated metal ratios in CSF include Cd/Se (p = 0.031), and 16 ratios with magnesium, such as Mn/Mg (p = 0.005) and Al/Mg (p = 0.014).

Conclusion: Metal ratios may be used as biomarkers in ALS diagnosis and as guidelines for preventive measures.

Nyckelord
Neurodegeneration, Neurotoxicity, Neuroprotection, Ratio, Metal exposure
Nationell ämneskategori
Neurologi Kemi
Identifikatorer
urn:nbn:se:su:diva-217137 (URN)10.1016/j.jtemb.2023.127163 (DOI)000972390800001 ()37004478 (PubMedID)2-s2.0-85151351858 (Scopus ID)
Tillgänglig från: 2023-05-17 Skapad: 2023-05-17 Senast uppdaterad: 2023-05-17Bibliografiskt granskad
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.
Öppna denna publikation i ny flik eller fönster >>Residue-specific binding of Ni(II) ions influences the structure and aggregation of amyloid beta (Aβ) peptides
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2023 (Engelska)Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 13, nr 1, artikel-id 3341Artikel i tidskrift (Refereegranskat) 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.

Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
urn:nbn:se:su:diva-229707 (URN)10.1038/s41598-023-29901-5 (DOI)000986236800026 ()36849796 (PubMedID)
Tillgänglig från: 2024-05-29 Skapad: 2024-05-29 Senast uppdaterad: 2024-05-29Bibliografiskt granskad
Berntsson, E., Sardis, M., Noormägi, A., Jarvet, J., Roos, P. M., Töugu, V., . . . Wärmländer, S. K. .. (2022). Mercury Ion Binding to Apolipoprotein E Variants ApoE2, ApoE3, and ApoE4: Similar Binding Affinities but Different Structure Induction Effects. ACS Omega, 7(33), 28924-28931
Öppna denna publikation i ny flik eller fönster >>Mercury Ion Binding to Apolipoprotein E Variants ApoE2, ApoE3, and ApoE4: Similar Binding Affinities but Different Structure Induction Effects
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2022 (Engelska)Ingår i: ACS Omega, E-ISSN 2470-1343, Vol. 7, nr 33, s. 28924-28931Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Mercury intoxication typically produces more severe outcomes in people with the APOE-ε4 gene, which codes for the ApoE4 variant of apolipoprotein E, compared to individuals with the APOE-ε2 and APOE-ε3 genes. Why the APOE-ε4 allele is a risk factor in mercury exposure remains unknown. One proposed possibility is that the ApoE protein could be involved in clearing of heavy metals, where the ApoE4 protein might perform this task worse than the ApoE2 and ApoE3 variants. Here, we used fluorescence and circular dichroism spectroscopies to characterize the in vitro interactions of the three different ApoE variants with Hg(I) and Hg(II) ions. Hg(I) ions displayed weak binding to all ApoE variants and induced virtually no structural changes. Thus, Hg(I) ions appear to have no biologically relevant interactions with the ApoE protein. Hg(II) ions displayed stronger and very similar binding affinities for all three ApoE isoforms, with KD values of 4.6 μM for ApoE2, 4.9 μM for ApoE3, and 4.3 μM for ApoE4. Binding of Hg(II) ions also induced changes in ApoE superhelicity, that is, altered coil–coil interactions, which might modify the protein function. As these structural changes were most pronounced in the ApoE4 protein, they could be related to the APOE-ε4 gene being a risk factor in mercury toxicity.

Nationell ämneskategori
Kemi
Identifikatorer
urn:nbn:se:su:diva-209191 (URN)10.1021/acsomega.2c02254 (DOI)000846759000001 ()36033665 (PubMedID)
Tillgänglig från: 2022-09-19 Skapad: 2022-09-19 Senast uppdaterad: 2022-09-19Bibliografiskt granskad
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
Öppna denna publikation i ny flik eller fönster >>Lithium ions display weak interaction with amyloid-beta (Aβ) peptides and have minor effects on their aggregation
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2021 (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.

Nyckelord
Alzheimer's disease, protein aggregation, metal-protein binding, neurodegeneration, pharmaceutics
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
urn:nbn:se:su:diva-196438 (URN)10.18388/abp.2020_5493 (DOI)000659435200003 ()33909969 (PubMedID)
Tillgänglig från: 2021-09-08 Skapad: 2021-09-08 Senast uppdaterad: 2022-10-11Bibliografiskt granskad
Koski, L., Ronnevi, C., Berntsson, E., Wärmländer, S. K. T. & Roos, P. M. (2021). Metals in ALS TDP-43 Pathology. International Journal of Molecular Sciences, 22(22), Article ID 12193.
Öppna denna publikation i ny flik eller fönster >>Metals in ALS TDP-43 Pathology
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2021 (Engelska)Ingår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, nr 22, artikel-id 12193Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

Amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease and similar neurodegenerative disorders take their toll on patients, caregivers and society. A common denominator for these disorders is the accumulation of aggregated proteins in nerve cells, yet the triggers for these aggregation processes are currently unknown. In ALS, protein aggregation has been described for the SOD1, C9orf72, FUS and TDP-43 proteins. The latter is a nuclear protein normally binding to both DNA and RNA, contributing to gene expression and mRNA life cycle regulation. TDP-43 seems to have a specific role in ALS pathogenesis, and ubiquitinated and hyperphosphorylated cytoplasmic inclusions of aggregated TDP-43 are present in nerve cells in almost all sporadic ALS cases. ALS pathology appears to include metal imbalances, and environmental metal exposure is a known risk factor in ALS. However, studies on metal-to-TDP-43 interactions are scarce, even though this protein seems to have the capacity to bind to metals. This review discusses the possible role of metals in TDP-43 aggregation, with respect to ALS pathology.

Nyckelord
neurodegeneration, proteinopathy, metallopathy, protein aggregation, amyloid, metal exposure, metal-protein binding
Nationell ämneskategori
Biologiska vetenskaper Neurovetenskaper
Identifikatorer
urn:nbn:se:su:diva-199535 (URN)10.3390/ijms222212193 (DOI)000724356100001 ()34830074 (PubMedID)
Tillgänglig från: 2021-12-15 Skapad: 2021-12-15 Senast uppdaterad: 2022-02-25Bibliografiskt granskad
Organisationer
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0002-7544-092X

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