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Jonsson, P. Andreas
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Publications (9 of 9) Show all publications
Bergh, J., Zetterström, P., Andersen, P. M., Brännström, T., Graffmo, K. S., Jonsson, P. A., . . . Marklund, S. (2015). Structural and kinetic analysis of protein-aggregate strains in vivo using binary epitope mapping. Proceedings of the National Academy of Sciences of the United States of America, 112(14), 4489-4494
Open this publication in new window or tab >>Structural and kinetic analysis of protein-aggregate strains in vivo using binary epitope mapping
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2015 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 14, p. 4489-4494Article in journal (Refereed) Published
Abstract [en]

Despite considerable progress in uncovering the molecular details of protein aggregation in vitro, the cause and mechanism of protein-aggregation disease remain poorly understood. One reason is that the amount of pathological aggregates in neural tissue is exceedingly low, precluding examination by conventional approaches. We present here a method for determination of the structure and quantity of aggregates in small tissue samples, circumventing the above problem. The method is based on binary epitope mapping using anti-peptide antibodies. We assessed the usefulness and versatility of the method in mice modeling the neurodegenerative disease amyotrophic lateral sclerosis, which accumulate intracellular aggregates of superoxide dismutase-1. Two strains of aggregates were identified with different structural architectures, molecular properties, and growth kinetics. Both were different from superoxide dismutase-1 aggregates generated in vitro under a variety of conditions. The strains, which seem kinetically under fragmentation control, are associated with different disease progressions, complying with and adding detail to the growing evidence that seeding, infectivity, and strain dependence are unifying principles of neurodegenerative disease.

Place, publisher, year, edition, pages
National Academy of Sciences, 2015
Keywords
protein aggregation, neurodegeneration, strain, amyotrophic lateral sclerosis, transgenic mice
National Category
Pharmacology and Toxicology Medical Bioscience
Identifiers
urn:nbn:se:umu:diva-103147 (URN)10.1073/pnas.1419228112 (DOI)000352287800075 ()25802384 (PubMedID)
Available from: 2015-05-28 Created: 2015-05-18 Last updated: 2018-08-19Bibliographically approved
Birve, A., Neuwirth, C., Weber, M., Marklund, S. L., Nilsson, A.-C., Jonsson, P. A. & Andersen, P. M. (2010). A novel SOD1 splice site mutation associated with familial ALS revealed by SOD activity analysis. Human Molecular Genetics, 19(21), 4201-4206
Open this publication in new window or tab >>A novel SOD1 splice site mutation associated with familial ALS revealed by SOD activity analysis
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2010 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 19, no 21, p. 4201-4206Article in journal (Refereed) Published
Abstract [en]

More than 145 mutations have been found in the gene CuZn-Superoxide dismutase (SOD1) in patients with amyotrophic lateral sclerosis (ALS). The vast majority are easily detected nucleotide mutations in the coding region. In a patient from a Swiss ALS family with half-normal erythrocyte SOD1 activity, exon flanking sequence analysis revealed a novel thymine to guanine mutation 7 bp upstream of exon 4 (c.240-7T>G). The results of splicing algorithm analyses were ambiguous, but five out of seven analysis tools suggested a potential novel splice site that would add six new base pairs to the mRNA. If translated, this mRNA would insert Ser and Ile between Glu78 and Arg79 in the SOD1 protein. In fibroblasts from the patient, the predicted mutant transcript and the mutant protein were both highly expressed, and despite the location of the insertion into the metal ion-binding loop IV, the SOD1 activity appeared high. In erythrocytes, which lack protein synthesis and are old compared with cultured fibroblasts, both SOD1 protein and enzymic activity was 50% of controls. Thus, the usage of the novel splice site is near 100%, and the mutant SOD1 shows the reduced stability typical of ALS-associated mutant SOD1s. The findings suggests that this novel intronic mutation is causing the disease and highlights the importance of wide exon-flanking sequencing and transcript analysis combined with erythrocyte SOD1 activity analysis in comprehensive search for SOD1 mutations in ALS. We find that there are potentially more SOD1 mutations than previously reported.

Keywords
ALS
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-40729 (URN)10.1093/hmg/ddq338 (DOI)000282751500007 ()20709807 (PubMedID)
Available from: 2011-03-08 Created: 2011-03-08 Last updated: 2018-06-08Bibliographically approved
Forsberg, K., Jonsson, P. A., Andersen, P. M., Bergemalm, D., Graffmo, K. S., Hultdin, M., . . . Brännström, T. (2010). Novel antibodies reveal inclusions containing non-native SOD1 in sporadic ALS patients. PLoS ONE, 5(7), e11552
Open this publication in new window or tab >>Novel antibodies reveal inclusions containing non-native SOD1 in sporadic ALS patients
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2010 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 7, p. e11552-Article in journal (Refereed) Published
Abstract [en]

Mutations in CuZn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) and are found in 6% of ALS patients. Non-native and aggregation-prone forms of mutant SOD1s are thought to trigger the disease. Two sets of novel antibodies, raised in rabbits and chicken, against peptides spaced along the human SOD1 sequence, were by enzyme-linked immunosorbent assay and an immunocapture method shown to be specific for denatured SOD1. These were used to examine SOD1 in spinal cords of ALS patients lacking mutations in the enzyme. Small granular SOD1-immunoreactive inclusions were found in spinal motoneurons of all 37 sporadic and familial ALS patients studied, but only sparsely in 3 of 28 neurodegenerative and 2 of 19 non-neurological control patients. The granular inclusions were by confocal microscopy found to partly colocalize with markers for lysosomes but not with inclusions containing TAR DNA binding protein-43, ubiquitin or markers for endoplasmic reticulum, autophagosomes or mitochondria. Granular inclusions were also found in carriers of SOD1 mutations and in spinobulbar muscular atrophy (SBMA) patients and they were the major type of inclusion detected in ALS patients homozygous for the wild type-like D90A mutation. The findings suggest that SOD1 may be involved in ALS pathogenesis in patients lacking mutations in the enzyme.

Place, publisher, year, edition, pages
Public library of science, 2010
Keywords
amyotrophic-lateral-sclerosis; cu/zn superoxide-dismutase; motor-neuron degeneration; molecular pathology; gene mutation; linked SOD1; mutant SOD1; mice; disease; immunoreactivity
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-40739 (URN)10.1371/journal.pone.0011552 (DOI)000279884900009 ()20644736 (PubMedID)
Available from: 2011-03-08 Created: 2011-03-08 Last updated: 2018-06-08Bibliographically approved
Bergemalm, D., Forsberg, K., Jonsson, P. A., Graffmo, K. S., Brännström, T., Andersen, P. M., . . . Marklund, S. L. (2009). Changes in the spinal cord proteome of an amyotrophic lateral sclerosis murine model determined by differential in-gel electrophoresis. Molecular and cellular proteomics, 8(6), 1306-1317
Open this publication in new window or tab >>Changes in the spinal cord proteome of an amyotrophic lateral sclerosis murine model determined by differential in-gel electrophoresis
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2009 (English)In: Molecular and cellular proteomics, ISSN 1535-9484, Vol. 8, no 6, p. 1306-1317Article in journal (Refereed) Published
Abstract [en]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of motor neurons resulting in progressive paralysis. To date, more than 140 different mutations in the gene encoding CuZn-superoxide dismutase (SOD1) have been associated with ALS. Several transgenic murine models exist in which various mutant SOD1s are expressed. We have used differential in-gel electrophoresis (DIGE) to analyze the changes in the spinal cord proteome induced by expression of the unstable SOD1 truncation mutant G127insTGGG (G127X) in mice. Unlike mutants used in most other models, G127X lacks SOD activity and is present at low levels, thus reducing the risk of overexpression artifacts. The mice were analyzed at their peak body weights, just before onset of symptoms. Variable importance plot (VIP) analysis showed that 420 of 1,800 detected protein spots contributed significantly to the differences between the groups. By MALDI-TOF MS analysis, 54 proteins were identified. One spot was found to be a covalently linked mutant SOD1 dimer, apparently analogous to SOD1 immunoreactive bands migrating at double the molecular weight of SOD1 monomers previously detected in humans and mice carrying mutant SOD1s and in sporadic ALS cases. Analyses of affected functional pathways, and the subcellular representation of alterations suggest that the toxicity exerted by mutant SODs induces oxidative stress and affects mitochondria, cellular assembly/organization, and protein degradation.

Place, publisher, year, edition, pages
The American Society for Biochemistry and Molecular Biology,Inc, 2009
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-22132 (URN)10.1074/mcp.M900046-MCP200 (DOI)19357085 (PubMedID)
Available from: 2009-04-24 Created: 2009-04-24 Last updated: 2018-06-08Bibliographically approved
Söderberg, J., Wallin, O., Jonsson, P. A., Brulin, C. & Grankvist, K. (2009). Comment on the letter to the editor ‘The importance of incident reporting in laboratory diagnosics’ by Lippi and Plebani.
Open this publication in new window or tab >>Comment on the letter to the editor ‘The importance of incident reporting in laboratory diagnosics’ by Lippi and Plebani
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2009 (English)Other (Other academic)
Identifiers
urn:nbn:se:umu:diva-34646 (URN)
Note
Kommentar till artikel: "The importance of incident reporting in laboratory diagnosics" by Giuseppe Lippi and Mario Plebani i tidskriften Scandinavian journal of clinical & laboratory investigation år 2009, vol 69, nr 8, sid 811-814.Available from: 2010-06-10 Created: 2010-06-10 Last updated: 2018-06-08Bibliographically approved
Wallin, O., Söderberg, J., Grankvist, K., Jonsson, A. & Hultdin, J. (2009). Preanalytical effects of pneumatic tube transport on routine haematology, coagulation parameters, platelet function and global coagulation. Clinical Chemistry and Laboratory Medicine, 46(10), 1443-1449
Open this publication in new window or tab >>Preanalytical effects of pneumatic tube transport on routine haematology, coagulation parameters, platelet function and global coagulation
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2009 (English)In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 46, no 10, p. 1443-1449Article in journal (Refereed) Published
Abstract [en]

Background: Pneumatic tube transport of blood samples reduces turnaround times and labour. However, the preanalytical effects on new clinical chemistry parameters and instruments are not fully known. The aim of this study was to evaluate the effect of pneumatic tube transport on haematology and coagulation parameters, including platelet function with PFA-100®, and global coagulation with a thromboelastograph.

Methods: Paired venous blood samples from healthy volunteers were obtained before and after 1 week of treatment with acetylsalicylic acid. One sample was transported by pneumatic tube transport, while the other remained in the laboratory.

Results: No preanalytical effect of pneumatic tube transport could be seen for most haematology and coagulation parameters, as well as analysis with PFA-100®. For the thromboelastographic analysis, time to clot formation was shorter (–16%, p=0.037) in the transported samples. Treatment with acetylsalicylic acid had no effect on the majority of the test results.

Conclusions: Pneumatic tube transport does not introduce preanalytical errors when transporting samples for analysis of routine haematology, coagulation parameters and platelet function with the PFA-100®. We recommend manual transport of samples for analysis with thromboelastographic techniques.

Keywords
platelet function anlysis, pneumatic tube transport, preanaltical, thromboelastograph, venous blood specimen
Identifiers
urn:nbn:se:umu:diva-3263 (URN)10.1515/CCLM.2008.288 (DOI)18844500 (PubMedID)
Available from: 2008-05-21 Created: 2008-05-21 Last updated: 2018-06-09Bibliographically approved
Jonsson, P. A., Graffmo, K. S., Andersen, P. M., Marklund, S. L. & Brännström, T. (2009). Superoxide dismutase in amyotrophic lateral sclerosis patients homozygous for the D90A mutation. Neurobiology of Disease, 36(3), 421-424
Open this publication in new window or tab >>Superoxide dismutase in amyotrophic lateral sclerosis patients homozygous for the D90A mutation
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2009 (English)In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 36, no 3, p. 421-424Article in journal (Refereed) Published
Abstract [en]

The most common of the amyotrophic lateral sclerosis (ALS)-associated superoxide dismutase-1 (SOD1) mutations, D90A, differs from others in its high structural stability and by the existence of both recessive and dominant inheritance. Here SOD1 in CNS and peripheral organs from five ALS patients homozygous for D90A were compared to controls. In most areas, including ventral horns, there were no significant differences in SOD1 activities and Western blotting patterns between controls and D90A cases. The SOD1 activities in areas vulnerable to mutant SOD1s, ventral horns and precentral gyrus were intermediate among CNS areas and much lower than in kidney and liver. Thus, the vulnerability of motor areas is not explained by high SOD1 content. The findings argue against the idea of expression-reducing protective factors being present near the D90A locus in recessive pedigrees. The similarity to wild-type SOD1 prompts speculations on the involvement of the latter in sporadic ALS.

National Category
Clinical Medicine Neurology
Identifiers
urn:nbn:se:umu:diva-34682 (URN)10.1016/j.nbd.2009.08.006 (DOI)000271689400002 ()19703565 (PubMedID)
Available from: 2010-06-11 Created: 2010-06-11 Last updated: 2018-06-08Bibliographically approved
Zetterström, P., Stewart, H. G., Bergemalm, D., Jonsson, P. A., Graffmo, K. S., Andersen, P. M., . . . Marklund, S. L. (2007). Soluble misfolded subfractions of mutant superoxide dismutase-1s are enriched in spinal cords throughout life in murine ALS models. Proceedings of the National Academy of Sciences of the United States of America, 104(35), 14157-14162
Open this publication in new window or tab >>Soluble misfolded subfractions of mutant superoxide dismutase-1s are enriched in spinal cords throughout life in murine ALS models
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2007 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 104, no 35, p. 14157-14162Article in journal (Refereed) Published
Abstract [en]

Mutants of superoxide dismutase-1 (SOD1) cause ALS by an unidentified cytotoxic mechanism. We have previously shown that the stable SOD1 mutants D90A and G93A are abundant and show the highest levels in liver and kidney in transgenic murine ALS models, whereas the unstable G85R and G127X mutants are scarce but enriched in the CNS. These data indicated that minute amounts of misfolded SOD1 enriched in the motor areas might exert the ALS-causing cytotoxicity. A hydrophobic interaction chromatography (HIC) protocol was developed with the aim to determine the abundance of soluble misfolded SOD1 in tissues in vivo. Most G85R and G127X mutant SOD1s bound in the assay, but only minute subfractions of the D90A and G93A mutants. The absolute levels of HIC-binding SOD1 were, however, similar and broadly inversely related to lifespans in the models. They were generally enriched in the susceptible spinal cord. The HIC-binding SOD1 was composed of disulfide-reduced subunits lacking metal ions and also subunits that apparently carried nonnative intrasubunit disulfide bonds. The levels were high from birth until death and were comparable to the amounts of SOD1 that become sequestered in aggregates in the terminal stage. The HIC-binding SOD1 species ranged from monomeric to trimeric in size. These species form a least common denominator amongst SOD1 mutants with widely different molecular characteristics and might be involved in the cytotoxicity that causes ALS.

Keywords
Animals, Disease Models; Animal, Humans, Mice, Mice; Transgenic, Motor Neuron Disease/enzymology/*genetics, Mutation, Oxidation-Reduction, Protein Denaturation, Protein Folding, Protein Subunits, Sequence Deletion, Spinal Cord/growth & development/*physiopathology, Superoxide Dismutase/*genetics/metabolism, Variation (Genetics)
Identifiers
urn:nbn:se:umu:diva-7589 (URN)10.1073/pnas.0700477104 (DOI)17715066 (PubMedID)
Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2018-06-09Bibliographically approved
Rudolfsson, S. H., Wikström, P., Jonsson, A., Collin, O. & Bergh, A. (2004). Hormonal regulation and functional role of vascular endothelial growth factor a in the rat testis.. Biol Reprod, 70(2), 340-7
Open this publication in new window or tab >>Hormonal regulation and functional role of vascular endothelial growth factor a in the rat testis.
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2004 (English)In: Biol Reprod, ISSN 0006-3363, Vol. 70, no 2, p. 340-7Article in journal (Refereed) Published
Keywords
Animals, Capillary Permeability/drug effects/physiology, Chorionic Gonadotropin/pharmacology, Male, Piperidines/pharmacology, Quinazolines/pharmacology, RNA; Messenger/analysis, Rats, Rats; Sprague-Dawley, Signal Transduction/drug effects/physiology, Testis/*blood supply/drug effects/*physiology, Vascular Endothelial Growth Factor A/*genetics/*metabolism/pharmacology, Vascular Endothelial Growth Factor Receptor-1/genetics/metabolism, Vascular Endothelial Growth Factor Receptor-2/genetics/metabolism
Identifiers
urn:nbn:se:umu:diva-14219 (URN)14561656 (PubMedID)
Available from: 2007-09-14 Created: 2007-09-14 Last updated: 2018-06-09Bibliographically approved
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