{"entity": "journal", "iuid": "840103a371c14d7dbb68be8f9298439e", "timestamp": "2026-08-11T08:25:12.621Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/ACS%20Chem%20Neurosci.json"}, "display": {"href": "https://publications.scilifelab.se/journal/ACS%20Chem%20Neurosci"}}, "title": "ACS Chem Neurosci", "issn": "1948-7193", "issn-l": "1948-7193", "publications_count": 13, "publications": [{"entity": "publication", "iuid": "de5f9b658ce74f6096b9c352ea946d5b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/de5f9b658ce74f6096b9c352ea946d5b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/de5f9b658ce74f6096b9c352ea946d5b"}}, "title": "SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF Resulting in Drastic Soluble Protein Depletion.", "authors": [{"family": "Christ", "given": "Wanda", "initials": "W", "orcid": "0000-0003-3886-5248", "researcher": {"href": "https://publications.scilifelab.se/researcher/38fe3a44fdb547b885cce5b6f490b2bc.json"}}, {"family": "Kapell", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-9304-558X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cffd944f88e54ed6a910183ba49ef656.json"}}, {"family": "Sobkowiak", "given": "Michal J", "initials": "MJ", "orcid": "0000-0003-2932-1994", "researcher": {"href": "https://publications.scilifelab.se/researcher/14f1eb990edf472cac56f24d7cae330c.json"}}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Evertsson", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Sork", "given": "Helena", "initials": "H", "orcid": "0000-0002-5390-4420", "researcher": {"href": "https://publications.scilifelab.se/researcher/f5d08dad4f2d4ee0a3e3a8f060383da5.json"}}, {"family": "Saher", "given": "Osama", "initials": "O"}, {"family": "Bazaz", "given": "Safa", "initials": "S"}, {"family": "Gustafsson", "given": "Oskar", "initials": "O"}, {"family": "Cardenas", "given": "Eduardo I", "initials": "EI"}, {"family": "Villa", "given": "Viviana", "initials": "V"}, {"family": "Ricciarelli", "given": "Roberta", "initials": "R"}, {"family": "Sandberg", "given": "Johan K", "initials": "JK", "orcid": "0000-0002-6275-0750", "researcher": {"href": "https://publications.scilifelab.se/researcher/7468c415a46645a3a4c3d28badcff954.json"}}, {"family": "Bergquist", "given": "Jonas", "initials": "J", "orcid": "0000-0002-4597-041X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d745034529f3423abbea230b4e586d20.json"}}, {"family": "Sturchio", "given": "Andrea", "initials": "A"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}, {"family": "Malm", "given": "Tarja", "initials": "T", "orcid": "0000-0002-9530-7472", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1ab3c9695424308b07c375901a089f4.json"}}, {"family": "Espay", "given": "Alberto J", "initials": "AJ"}, {"family": "Pernemalm", "given": "Maria", "initials": "M", "orcid": "0000-0003-4624-031X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f15f303cb2044cfa81719700137e3603.json"}}, {"family": "Lind\u00e9n", "given": "Anders", "initials": "A"}, {"family": "Klingstr\u00f6m", "given": "Jonas", "initials": "J", "orcid": "0000-0001-9076-1441", "researcher": {"href": "https://publications.scilifelab.se/researcher/95c1b345ae434fb383b7fe6a1d053c80.json"}}, {"family": "El Andaloussi", "given": "Samir", "initials": "S", "orcid": "0000-0003-4468-9113", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd1036a42043441da3e444f4eac58010.json"}}, {"family": "Ezzat", "given": "Kariem", "initials": "K", "orcid": "0000-0003-4186-0675", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f2f1d3d8a5d467c8fc3b95388e4c606.json"}}], "type": "journal article", "published": "2024-11-20", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "15", "issue": "22", "pages": "4095-4104", "issn-l": "1948-7193"}, "abstract": "The corona virus (SARS-CoV-2) pandemic and the resulting long-term neurological complications in patients, known as long COVID, have renewed interest in the correlation between viral infections and neurodegenerative brain disorders. While many viruses can reach the central nervous system (CNS) causing acute or chronic infections (such as herpes simplex virus 1, HSV-1), the lack of a clear mechanistic link between viruses and protein aggregation into amyloids, a characteristic of several neurodegenerative diseases, has rendered such a connection elusive. Recently, we showed that viruses can induce aggregation of purified amyloidogenic proteins via the direct physicochemical mechanism of heterogeneous nucleation (HEN). In the current study, we show that the incubation of HSV-1 and SARS-CoV-2 with human cerebrospinal fluid (CSF) leads to the amyloid aggregation of several proteins known to be involved in neurodegenerative diseases, such as APLP1 (amyloid \u03b2 precursor like protein 1), ApoE, clusterin, \u03b12-macroglobulin, PGK-1 (phosphoglycerate kinase 1), ceruloplasmin, nucleolin, 14-3-3, transthyretin, and vitronectin. Importantly, UV-inactivation of SARS-CoV-2 does not affect its ability to induce amyloid aggregation, as amyloid formation is dependent on viral surface catalysis via HEN and not its ability to replicate. Additionally, viral amyloid induction led to a dramatic drop in the soluble protein concentration in the CSF. Our results show that viruses can physically induce amyloid aggregation of proteins in human CSF and result in soluble protein depletion, thus providing a potential mechanism that may account for the association between persistent and latent/reactivating brain infections and neurodegenerative diseases.", "doi": "10.1021/acschemneuro.4c00636", "pmid": "39510798", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Global Proteomics and Proteogenomics": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2024-11-15T09:02:02.653Z", "modified": "2025-04-07T07:30:58.294Z"}, {"entity": "publication", "iuid": "9717ba8e95f14c378df3396d352f6874", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9717ba8e95f14c378df3396d352f6874.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9717ba8e95f14c378df3396d352f6874"}}, "title": "Hypoxic-Ischemic Insult Alters Polyamine and Neurotransmitter Abundance in the Specific Neonatal Rat Brain Subregions.", "authors": [{"family": "M\u00e1cha", "given": "Hynek", "initials": "H"}, {"family": "Lupt\u00e1kov\u00e1", "given": "Dominika", "initials": "D"}, {"family": "Jur\u00e1nek", "given": "Ivo", "initials": "I"}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE"}, {"family": "Havl\u00ed\u010dek", "given": "Vladim\u00edr", "initials": "V", "orcid": "0000-0002-8614-7059", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2c52ec2b93e46349d031e7b15053e37.json"}}], "type": "journal article", "published": "2024-08-07", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "15", "issue": "15", "pages": "2811-2821", "issn-l": "1948-7193"}, "abstract": "Neonatal hypoxic-ischemic (HI) brain insult is a major cause of neonatal mortality and morbidity. To assess the underlying pathological mechanisms, we mapped the spatiotemporal changes in polyamine, amino acid, and neurotransmitter levels, following HI insult (by the Rice-Vannucci method) in the brains of seven-day-old rat pups. Matrix-assisted laser desorption/ionization mass spectrometry imaging of chemically modified small-molecule metabolites by 4-(anthracen-9-yl)-2-fluoro-1-methylpyridin-1-ium iodide revealed critical HI-related metabolomic changes of 22 metabolites in 14 rat brain subregions, much earlier than light microscopy detected signs of neuronal damage. For the first time, we demonstrated excessive polyamine oxidation and accumulation of 3-aminopropanal in HI neonatal brains, which was later accompanied by neuronal apoptosis enhanced by increases in glycine and norepinephrine in critically affected brain regions. Specifically, putrescine, cadaverine, and 3-aminopropanal increased significantly as early as 12 h postinsult, mainly in motor and somatosensory cortex, hippocampus, and midbrain, followed by an increase in norepinephrine 24 h postinsult, which was predominant in the caudate putamen, the region most vulnerable to HI. The decrease of \u03b3-aminobutyric acid (GABA) and the continuous dysregulation of the GABAergic system together with low taurine levels up to 36 h sustained progressive neurodegenerative cellular processes. The molecular alterations presented here at the subregional rat brain level provided unprecedented insight into early metabolomic changes in HI-insulted neonatal brains, which may further aid in the identification of novel therapeutic targets for the treatment of neonatal HI encephalopathy.", "doi": "10.1021/acschemneuro.4c00190", "pmid": "39058922", "labels": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11311127"}], "notes": [], "created": "2024-11-20T10:42:32.820Z", "modified": "2024-11-20T10:42:32.947Z"}, {"entity": "publication", "iuid": "ad5916e84efd42529a1c95bb30f10292", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ad5916e84efd42529a1c95bb30f10292.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ad5916e84efd42529a1c95bb30f10292"}}, "title": "Applying Spatial Metabolomics To Investigate Age- and Drug-Induced Neurochemical Changes.", "authors": [{"family": "Vallianatou", "given": "Theodosia", "initials": "T", "orcid": "0000-0002-1477-7756", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae610b7669754328a119654fdfcd6af4.json"}}, {"family": "Angerer", "given": "Tina B", "initials": "TB", "orcid": "0000-0003-3852-6254", "researcher": {"href": "https://publications.scilifelab.se/researcher/c3f5ed541c9f4e2bb6c7c7519d6ad36b.json"}}, {"family": "Kaya", "given": "Ibrahim", "initials": "I"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Shariatgorji", "given": "Reza", "initials": "R"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f6381de42949db8d30b56b526f3e26.json"}}], "type": "journal article", "published": "2024-08-07", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "15", "issue": "15", "pages": "2822-2829", "issn-l": "1948-7193"}, "abstract": "In an era when population aging is increasing the burden of neurodegenerative conditions, deciphering the mechanisms underlying brain senescence is more important than ever. Here, we present a spatial metabolomics analysis of age-induced neurochemical alterations in the mouse brain using negative ionization mode mass spectrometry imaging. The age-dependent effects of the acetylcholinesterase inhibitor tacrine were simultaneously examined. For ultrahigh mass resolution analysis, we utilized a Fourier-transform ion cyclotron resonance spectrometer. To complement this, a trapped ion mobility spectrometry time-of-flight analyzer provided high speed and lateral resolution. The chosen approach facilitated the detection and identification of a wide range of metabolites, from amino acids to sphingolipids. We reported significant, age-dependent alterations in brain lipids which were most evident for sulfatides and lysophosphatidic acids. Sulfatide species, which are mainly localized to white matter, either increased or decreased with age, depending on the carbon chain length and hydroxylation stage. Lysophosphatidic acids were found to decrease with age in the detailed cortical and hippocampal subregions. An age-dependent increase in the glutamine/glutamate ratio, an indicator of glia-neuron interconnection and neurotoxicity, was detected after tacrine administration. The presented metabolic mapping approach was able to provide visualizations of the lipid signaling and neurotransmission alterations induced by early aging and can thus be beneficial to further elucidating age-related neurochemical pathways.", "doi": "10.1021/acschemneuro.4c00199", "pmid": "39072364", "labels": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11311129"}], "notes": [], "created": "2024-11-20T10:41:26.891Z", "modified": "2024-11-20T10:41:27.370Z"}, {"entity": "publication", "iuid": "09455542a8094d369e78ac30b0583978", "links": {"self": {"href": "https://publications.scilifelab.se/publication/09455542a8094d369e78ac30b0583978.json"}, "display": {"href": "https://publications.scilifelab.se/publication/09455542a8094d369e78ac30b0583978"}}, "title": "A\u03b2 Oligomer Dissociation Is Catalyzed by Fibril Surfaces.", "authors": [{"family": "Dear", "given": "Alexander J", "initials": "AJ", "orcid": "0000-0003-3055-607X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee81a5b392844ae18b6917d666f2ae72.json"}}, {"family": "Thacker", "given": "Dev", "initials": "D", "orcid": "0000-0001-6171-9703", "researcher": {"href": "https://publications.scilifelab.se/researcher/738d6b0064e841eaab836983136e5cd4.json"}}, {"family": "Wennmalm", "given": "Stefan", "initials": "S"}, {"family": "Ortigosa-Pascual", "given": "Lei", "initials": "L", "orcid": "0000-0003-0656-9225", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e185a9314464ae7a7333cff01e701e9.json"}}, {"family": "Andrzejewska", "given": "Ewa A", "initials": "EA"}, {"family": "Meisl", "given": "Georg", "initials": "G", "orcid": "0000-0002-6562-7715", "researcher": {"href": "https://publications.scilifelab.se/researcher/b6c644b9883c4428b86d0033d823789f.json"}}, {"family": "Linse", "given": "Sara", "initials": "S", "orcid": "0000-0001-9629-7109", "researcher": {"href": "https://publications.scilifelab.se/researcher/423dc0e490a942b1ba364b08068b71d8.json"}}, {"family": "Knowles", "given": "Tuomas P J", "initials": "TPJ", "orcid": "0000-0002-7879-0140", "researcher": {"href": "https://publications.scilifelab.se/researcher/930a7475dae4421894a5c02d689988a7.json"}}], "type": "journal article", "published": "2024-06-05", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "15", "issue": "11", "pages": "2296-2307", "issn-l": "1948-7193"}, "abstract": "Oligomeric assemblies consisting of only a few protein subunits are key species in the cytotoxicity of neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. Their lifetime in solution and abundance, governed by the balance of their sources and sinks, are thus important determinants of disease. While significant advances have been made in elucidating the processes that govern oligomer production, the mechanisms behind their dissociation are still poorly understood. Here, we use chemical kinetic modeling to determine the fate of oligomers formed in vitro and discuss the implications for their abundance in vivo. We discover that oligomeric species formed predominantly on fibril surfaces, a broad class which includes the bulk of oligomers formed by the key Alzheimer's disease-associated A\u03b2 peptides, also dissociate overwhelmingly on fibril surfaces, not in solution as had previously been assumed. We monitor this \"secondary nucleation in reverse\" by measuring the dissociation of A\u03b242 oligomers in the presence and absence of fibrils via two distinct experimental methods. Our findings imply that drugs that bind fibril surfaces to inhibit oligomer formation may also inhibit their dissociation, with important implications for rational design of therapeutic strategies for Alzheimer's and other amyloid diseases.", "doi": "10.1021/acschemneuro.4c00127", "pmid": "38785363", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11157482"}], "notes": [], "created": "2024-11-25T17:41:21.423Z", "modified": "2025-11-13T14:12:41.792Z"}, {"entity": "publication", "iuid": "3778dd8279784fbfb3ef2e0fe7ceb521", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3778dd8279784fbfb3ef2e0fe7ceb521.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3778dd8279784fbfb3ef2e0fe7ceb521"}}, "title": "Spatial Neurolipidomics at the Single Amyloid-\u03b2 Plaque Level in Postmortem Human Alzheimer's Disease Brain.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W"}, {"family": "Bowman", "given": "Andrew", "initials": "A"}, {"family": "Jha", "given": "Durga", "initials": "D"}, {"family": "Minta", "given": "Karolina", "initials": "K"}, {"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Koutarapu", "given": "Srinivas", "initials": "S"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Lashley", "given": "Tammaryn", "initials": "T"}, {"family": "Heeren", "given": "Ron M A", "initials": "RMA", "orcid": "0000-0002-6533-7179", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e7bc52c5d4848aabb62bde4932efa1a.json"}}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2024-02-21", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "15", "issue": "4", "pages": "877-888", "issn-l": "1948-7193"}, "abstract": "Lipid dysregulations have been critically implicated in Alzheimer's disease (AD) pathology. Chemical analysis of amyloid-\u03b2 (A\u03b2) plaque pathology in transgenic AD mouse models has demonstrated alterations in the microenvironment in the direct proximity of A\u03b2 plaque pathology. In mouse studies, differences in lipid patterns linked to structural polymorphism among A\u03b2 pathology, such as diffuse, immature, and mature fibrillary aggregates, have also been reported. To date, no comprehensive analysis of neuronal lipid microenvironment changes in human AD tissue has been performed. Here, for the first time, we leverage matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) through a high-speed and spatial resolution commercial time-of-light instrument, as well as a high-mass-resolution in-house-developed orbitrap system to characterize the lipid microenvironment in postmortem human brain tissue from AD patients carrying Presenilin 1 mutations (PSEN1) that lead to familial forms of AD (fAD). Interrogation of the spatially resolved MSI data on a single A\u03b2 plaque allowed us to verify nearly 40 sphingolipid and phospholipid species from diverse subclasses being enriched and depleted, in relation to the A\u03b2 deposits. This included monosialo-gangliosides (GM), ceramide monohexosides (HexCer), ceramide-1-phosphates (CerP), ceramide phosphoethanolamine conjugates (PE-Cer), sulfatides (ST), as well as phosphatidylinositols (PI), phosphatidylethanolamines (PE), and phosphatidic acid (PA) species (including Lyso-forms). Indeed, many of the sphingolipid species overlap with the species previously seen in transgenic AD mouse models. Interestingly, in comparison to the animal studies, we observed an increased level of localization of PE and PI species containing arachidonic acid (AA). These findings are highly relevant, demonstrating for the first time A\u03b2 plaque pathology-related alteration in the lipid microenvironment in humans. They provide a basis for the development of potential lipid biomarkers for AD characterization and insight into human-specific molecular pathway alterations.", "doi": "10.1021/acschemneuro.4c00006", "pmid": "38299453", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10885149"}], "notes": [], "created": "2024-11-15T12:09:25.953Z", "modified": "2024-11-15T12:09:26.134Z"}, {"entity": "publication", "iuid": "7a8969678e1742c5b58d335eda1d3b55", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7a8969678e1742c5b58d335eda1d3b55.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7a8969678e1742c5b58d335eda1d3b55"}}, "title": "Omega-3 and -6 Fatty Acids Alter the Membrane Lipid Composition and Vesicle Size to Regulate Exocytosis and Storage of Catecholamines.", "authors": [{"family": "Gu", "given": "Chaoyi", "initials": "C"}, {"family": "Philipsen", "given": "Mai H", "initials": "MH"}, {"family": "Ewing", "given": "Andrew G", "initials": "AG", "orcid": "0000-0002-2084-0133", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6ecb82dc7a6423fa0876822f5568e1b.json"}}], "type": "journal article", "published": "2024-02-21", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "15", "issue": "4", "pages": "816-826", "issn-l": "1948-7193"}, "abstract": "The two essential fatty acids, alpha-linolenic acid and linoleic acid, and the higher unsaturated fatty acids synthesized from them are critical for the development and maintenance of normal brain functions. Deficiencies of these fatty acids have been shown to cause damage to the neuronal development, cognition, and locomotor function. We combined electrochemistry and imaging techniques to examine the effects of the two essential fatty acids on catecholamine release dynamics and the vesicle content as well as on the cell membrane phospholipid composition to understand how they impact exocytosis and by extension neurotransmission at the single-cell level. Incubation of either of the two fatty acids reduces the size of secretory vesicles and enables the incorporation of more double bonds into the cell membrane structure, resulting in higher membrane flexibility. This subsequently affects proteins regulating the dynamics of the exocytotic fusion pore and thereby affects exocytosis. Our data suggest a possible pathway whereby the two essential fatty acids affect the membrane structure to impact exocytosis and provide a potential treatment for diseases and impairments related to catecholamine signaling.", "doi": "10.1021/acschemneuro.3c00741", "pmid": "38344810", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10884999"}], "notes": [], "created": "2024-11-15T12:05:20.148Z", "modified": "2024-11-15T12:05:20.159Z"}, {"entity": "publication", "iuid": "54f28f56bbfa46e89278db2c23daf2c7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/54f28f56bbfa46e89278db2c23daf2c7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/54f28f56bbfa46e89278db2c23daf2c7"}}, "title": "Wide-Ranging Effects on the Brain Proteome in a Transgenic Mouse Model of Alzheimer's Disease Following Treatment with a Brain-Targeting Somatostatin Peptide.", "authors": [{"family": "Rofo", "given": "Fadi", "initials": "F"}, {"family": "Sandbaumh\u00fcter", "given": "Friederike A", "initials": "FA"}, {"family": "Chourlia", "given": "Aikaterini", "initials": "A"}, {"family": "Metzendorf", "given": "Nicole G", "initials": "NG"}, {"family": "Morrison", "given": "Jamie I", "initials": "JI"}, {"family": "Syv\u00e4nen", "given": "Stina", "initials": "S", "orcid": "0000-0002-8196-4041", "researcher": {"href": "https://publications.scilifelab.se/researcher/758608b82e734dd8a18b78723f0fc05c.json"}}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f6381de42949db8d30b56b526f3e26.json"}}, {"family": "Jansson", "given": "Erik T", "initials": "ET"}, {"family": "Hultqvist", "given": "Greta", "initials": "G", "orcid": "0000-0002-4136-6792", "researcher": {"href": "https://publications.scilifelab.se/researcher/759543bdff8a4b70a4edae45912015a6.json"}}], "type": "journal article", "published": "2021-07-07", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "issn-l": "1948-7193", "volume": "12", "issue": "13", "pages": "2529-2541"}, "abstract": "Alzheimer's disease is the most common neurodegenerative disorder characterized by the pathological aggregation of amyloid-\u03b2 (A\u03b2) peptide. A potential therapeutic intervention in Alzheimer's disease is to enhance A\u03b2 degradation by increasing the activity of A\u03b2-degrading enzymes, including neprilysin. The somatostatin (SST) peptide has been identified as an activator of neprilysin. Recently, we demonstrated the ability of a brain-penetrating SST peptide (SST-scFv8D3) to increase neprilysin activity and membrane-bound A\u03b242 degradation in the hippocampus of mice overexpressing the A\u03b2-precursor protein with the Swedish mutation (APPswe). Using LC-MS, we further evaluated the anti-Alzheimer's disease effects of SST-scFv8D3. Following a triple intravenous injection of SST-scFv8D3, the LC-MS analysis of the brain proteome revealed that the majority of downregulated proteins consisted of mitochondrial proteins regulating fatty acid oxidation, which are otherwise upregulated in APPswe mice compared to wild-type mice. Moreover, treatment with SST-scFv8D3 significantly increased hippocampal levels of synaptic proteins regulating cell membrane trafficking and neuronal development. Finally, hippocampal concentrations of growth-regulated \u03b1 (KC/GRO) chemokine and degradation of neuropeptide-Y were elevated after SST-scFv8D3 treatment. In summary, our results demonstrate a multifaceted effect profile in regulating mitochondrial function and neurogenesis following treatment with SST-scFv8D3, further suggesting the development of Alzheimer's disease therapies based on SST peptides.", "doi": "10.1021/acschemneuro.1c00303", "pmid": "34170117", "labels": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC8291608"}], "notes": [], "created": "2021-12-03T11:47:39.585Z", "modified": "2021-12-09T13:47:24.974Z"}, {"entity": "publication", "iuid": "7e76b41cc24d49e7aac02b1ad215dfaf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7e76b41cc24d49e7aac02b1ad215dfaf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7e76b41cc24d49e7aac02b1ad215dfaf"}}, "title": "Cooperativity of \u03b1-Synuclein Binding to Lipid Membranes.", "authors": [{"family": "Makasewicz", "given": "Katarzyna", "initials": "K", "orcid": "0000-0001-7224-5750", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca9cb98f0f9147f8ac78b53db78d2ec8.json"}}, {"family": "Wennmalm", "given": "Stefan", "initials": "S"}, {"family": "Stenqvist", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0002-9099-0663", "researcher": {"href": "https://publications.scilifelab.se/researcher/8febbffefa8e4602af87ed8166b72de5.json"}}, {"family": "Fornasier", "given": "Marco", "initials": "M"}, {"family": "Andersson", "given": "Alexandra", "initials": "A"}, {"family": "J\u00f6nsson", "given": "Peter", "initials": "P", "orcid": "0000-0003-2994-8017", "researcher": {"href": "https://publications.scilifelab.se/researcher/96df47b6279041939dfdc634f24179c2.json"}}, {"family": "Linse", "given": "Sara", "initials": "S", "orcid": "0000-0001-9629-7109", "researcher": {"href": "https://publications.scilifelab.se/researcher/423dc0e490a942b1ba364b08068b71d8.json"}}, {"family": "Sparr", "given": "Emma", "initials": "E", "orcid": "0000-0001-8343-9657", "researcher": {"href": "https://publications.scilifelab.se/researcher/7af3e5cb6d3a45fa888adad2fbaed1c2.json"}}], "type": "journal article", "published": "2021-06-16", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "12", "issue": "12", "pages": "2099-2109", "issn-l": "1948-7193"}, "abstract": "Cooperative binding is a key feature of metabolic pathways, signaling, and transport processes. It provides tight regulation over a narrow concentration interval of a ligand, thus enabling switching to be triggered by small concentration variations. The data presented in this work reveal strong positive cooperativity of \u03b1-synuclein binding to phospholipid membranes. Fluorescence cross-correlation spectroscopy, confocal microscopy, and cryo-TEM results show that in excess of vesicles \u03b1-synuclein does not distribute randomly but binds only to a fraction of all available vesicles. Furthermore, \u03b1-synuclein binding to a supported lipid bilayer observed with total internal reflection fluorescence microscopy displays a much steeper dependence of bound protein on total protein concentration than expected for independent binding. The same phenomenon was observed in the case of \u03b1-synuclein binding to unilamellar vesicles of sizes in the nm and \u03bcm range as well as to flat supported lipid bilayers, ruling out that nonuniform binding of the protein is governed by differences in membrane curvature. Positive cooperativity of \u03b1-synuclein binding to lipid membranes means that the affinity of the protein to a membrane is higher where there is already protein bound compared to a bare membrane. The phenomenon described in this work may have implications for \u03b1-synuclein function in synaptic transmission and other membrane remodeling events.", "doi": "10.1021/acschemneuro.1c00006", "pmid": "34076426", "labels": {"Integrated Microscopy Technologies Stockholm": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC8291482"}], "notes": [], "created": "2021-08-24T09:55:21.453Z", "modified": "2021-11-10T12:24:08.743Z"}, {"entity": "publication", "iuid": "1d98cc80efea4170b653e983cc7d9744", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d98cc80efea4170b653e983cc7d9744.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d98cc80efea4170b653e983cc7d9744"}}, "title": "Integration of Mass Spectrometry Imaging and Machine Learning Visualizes Region-Specific Age-Induced and Drug-Target Metabolic Perturbations in the Brain.", "authors": [{"family": "Vallianatou", "given": "Theodosia", "initials": "T", "orcid": "0000-0002-1477-7756", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae610b7669754328a119654fdfcd6af4.json"}}, {"family": "Shariatgorji", "given": "Reza", "initials": "R", "orcid": "0000-0001-9484-0921", "researcher": {"href": "https://publications.scilifelab.se/researcher/7762e9f6779c4780a4077c557eb7a3b6.json"}}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Karlgren", "given": "Maria", "initials": "M"}, {"family": "Hulme", "given": "Heather", "initials": "H"}, {"family": "Fridjonsdottir", "given": "Elva", "initials": "E"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f6381de42949db8d30b56b526f3e26.json"}}], "type": "journal article", "published": "2021-05-19", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "12", "issue": "10", "pages": "1811-1823", "issn-l": "1948-7193"}, "abstract": "Detailed metabolic imaging of specific brain regions in early aging may expose pathophysiological mechanisms and indicate effective neuropharmacological targets in the onset of cognitive decline. Comprehensive imaging of brain aging and drug-target effects is restricted using conventional methodology. We simultaneously visualized multiple metabolic alterations induced by normal aging in specific regions of mouse brains by integrating Fourier-transform ion cyclotron resonance mass spectrometry imaging and combined supervised and unsupervised machine learning models. We examined the interplay between aging and the response to tacrine-induced acetylcholinesterase inhibition, a well-characterized therapeutic treatment against dementia. The dipeptide carnosine (\u03b2-alanyl-l-histidine) and the vitamin \u03b1-tocopherol were significantly elevated by aging in different brain regions. l-Carnitine and acetylcholine metabolism were found to be major pathways affected by aging and tacrine administration in a brain region-specific manner, indicating altered mitochondrial function and neurotransmission. The highly interconnected hippocampus and retrosplenial cortex displayed different age-induced alterations in lipids and acylcarnitines, reflecting diverse region-specific metabolic effects. The subregional differences observed in the hippocampal formation of several lipid metabolites demonstrate the unique potential of the technique compared to standard mass spectrometry approaches. An age-induced increase of endogenous antioxidants, such as \u03b1-tocopherol, in the hippocampus was detected, suggesting an augmentation of neuroprotective mechanisms in early aging. Our comprehensive imaging approach visualized heterogeneous age-induced metabolic perturbations in mitochondrial function, neurotransmission, and lipid signaling, not always attenuated by acetylcholinesterase inhibition.", "doi": "10.1021/acschemneuro.1c00103", "pmid": "33939923", "labels": {"Spatial Mass Spectrometry": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC8291481"}], "notes": [], "created": "2021-12-03T11:49:03.306Z", "modified": "2021-12-03T11:49:03.347Z"}, {"entity": "publication", "iuid": "2b69e6724aad4404af9b681b04fdcb9d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2b69e6724aad4404af9b681b04fdcb9d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2b69e6724aad4404af9b681b04fdcb9d"}}, "title": "Interaction between Copper Chaperone Atox1 and Parkinson's Disease Protein \u03b1-Synuclein Includes Metal-Binding Sites and Occurs in Living Cells.", "authors": [{"family": "Horvath", "given": "Istvan", "initials": "I"}, {"family": "Blockhuys", "given": "St\u00e9phanie", "initials": "S"}, {"family": "\u0160ulskis", "given": "Darius", "initials": "D"}, {"family": "Holgersson", "given": "Stellan", "initials": "S"}, {"family": "Kumar", "given": "Ranjeet", "initials": "R"}, {"family": "Burmann", "given": "Bj\u00f6rn M", "initials": "BM"}, {"family": "Wittung-Stafshede", "given": "Pernilla", "initials": "P", "orcid": "0000-0003-1058-1964", "researcher": {"href": "https://publications.scilifelab.se/researcher/9016aa00d62f439fb15532a1f4ba814e.json"}}], "type": "journal article", "published": "2019-11-20", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "10", "issue": "11", "pages": "4659-4668", "issn-l": "1948-7193"}, "abstract": "Alterations in copper ion homeostasis appear coupled to neurodegenerative disorders, but mechanisms are unknown. The cytoplasmic copper chaperone Atox1 was recently found to inhibit amyloid formation in vitro of \u03b1-synuclein, the amyloidogenic protein in Parkinson's disease. As \u03b1-synuclein may have copper-dependent functions, and free copper ions promote \u03b1-synuclein amyloid formation, it is important to characterize the Atox1 interaction with \u03b1-synuclein on a molecular level. Here we applied solution-state nuclear magnetic resonance spectroscopy, with isotopically labeled \u03b1-synuclein and Atox1, to define interaction regions in both proteins. The \u03b1-synuclein interaction interface includes the whole N-terminal part up to Gln24; in Atox1, residues around the copper-binding cysteines (positions 11-16) are mostly perturbed, but additional effects are also found for residues elsewhere in both proteins. Because \u03b1-synuclein is N-terminally acetylated in vivo, we established that Atox1 also inhibits amyloid formation of this variant in vitro, and proximity ligation in human cell lines demonstrated \u03b1-synuclein-Atox1 interactions in situ. Thus, this interaction may provide the direct link between copper homeostasis and amyloid formation in vivo.", "doi": "10.1021/acschemneuro.9b00476", "pmid": "31600047", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-07T11:03:19.906Z", "modified": "2025-10-17T13:03:57.367Z"}, {"entity": "publication", "iuid": "8022a99f3bf947d5b23922574afb9d5d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8022a99f3bf947d5b23922574afb9d5d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8022a99f3bf947d5b23922574afb9d5d"}}, "title": "Cu/Zn Superoxide Dismutase Forms Amyloid Fibrils under Near-Physiological Quiescent Conditions: The Roles of Disulfide Bonds and Effects of Denaturant.", "authors": [{"family": "Khan", "given": "M Ashhar I", "initials": "MAI"}, {"family": "Respondek", "given": "Michal", "initials": "M"}, {"family": "Kjellstr\u00f6m", "given": "Sven", "initials": "S"}, {"family": "Deep", "given": "Shashank", "initials": "S"}, {"family": "Linse", "given": "Sara", "initials": "S"}, {"family": "Akke", "given": "Mikael", "initials": "M", "orcid": "0000-0002-2395-825X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e36b418e03154b90a8722670bed9e81a.json"}}], "type": "journal article", "published": "2017-09-20", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "8", "issue": "9", "pages": "2019-2026", "issn-l": "1948-7193"}, "abstract": "Cu/Zn superoxide dismutase (SOD1) forms intracellular aggregates that are pathological indicators of amyotrophic lateral sclerosis. A large body of research indicates that the entry point to aggregate formation is a monomeric, metal-ion free (apo), and disulfide-reduced species. Fibril formation by SOD1 in vitro has typically been reported only for harsh solvent conditions or mechanical agitation. Here we show that monomeric apo-SOD1 in the disulfide-reduced state forms fibrillar aggregates under near-physiological quiescent conditions. Monomeric apo-SOD1 with an intact intramolecular disulfide bond is highly resistant to aggregation under the same conditions. A cysteine-free variant of SOD1 exhibits fibrillization behavior and fibril morphology identical to those of disulfide-reduced SOD1, firmly establishing that intermolecular disulfide bonds or intramolecular disulfide shuffling are not required for aggregation and fibril formation. The decreased lag time for fibril formation resulting from reduction of the intramolecular disulfide bond thus primarily reflects the decreased stability of the folded state relative to partially unfolded states, rather than an active role of free sulfhydryl groups in mediating aggregation. Addition of urea to increase the amount of fully unfolded SOD1 increases the lag time for fibril formation, indicating that the population of this species does not dominate over other factors in determining the onset of aggregation. Our results contrast with previous results obtained for agitated samples, in which case amyloid formation was accelerated by denaturant. We reconcile these observations by suggesting that denaturants destabilize monomeric and aggregated species to different extents and thus affect nucleation and growth.", "doi": "10.1021/acschemneuro.7b00162", "pmid": "28585802", "labels": {"Structural Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1021/acschemneuro.7b00162"}], "notes": [], "created": "2020-01-27T10:04:14.767Z", "modified": "2021-06-16T10:21:21.392Z"}, {"entity": "publication", "iuid": "1e2f5f5b41994ebe87f808d019813e2c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1e2f5f5b41994ebe87f808d019813e2c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1e2f5f5b41994ebe87f808d019813e2c"}}, "title": "Delineating Amyloid Plaque Associated Neuronal Sphingolipids in Transgenic Alzheimer's Disease Mice (tgArcSwe) Using MALDI Imaging Mass Spectrometry.", "authors": [{"family": "Kaya", "given": "Ibrahim", "initials": "I"}, {"family": "Brinet", "given": "Dimitri", "initials": "D"}, {"family": "Michno", "given": "Wojciech", "initials": "W"}, {"family": "Syv\u00e4nen", "given": "Stina", "initials": "S"}, {"family": "Sehlin", "given": "Dag", "initials": "D"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2017-02-15", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "8", "issue": "2", "pages": "347-355", "issn-l": "1948-7193"}, "abstract": "The major pathological hallmarks of Alzheimer's disease (AD) are the progressive aggregation and accumulation of beta-amyloid (A\u03b2) and hyperphosphorylated tau protein into neurotoxic deposits. A\u03b2 aggregation has been suggested as the critical early inducer, driving the disease progression. However, the factors that promote neurotoxic A\u03b2 aggregation remain elusive. Imaging mass spectrometry (IMS) is a powerful technique to comprehensively elucidate the spatial distribution patterns of lipids, peptides, and proteins in biological tissue sections. In the present study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS)-based imaging was used on transgenic Alzheimer's disease mouse (tgArcSwe) brain tissue to investigate the sphingolipid microenvironment of individual A\u03b2 plaques and elucidate plaque-associated sphingolipid alterations. Multivariate data analysis was used to interrogate the IMS data for identifying pathologically relevant, anatomical features based on their lipid chemical profile. This approach revealed sphingolipid species that distinctly located to cortical and hippocampal deposits, whose A\u03b2 identity was further verified using fluorescent amyloid staining and immunohistochemistry. Subsequent multivariate statistical analysis of the spectral data revealed significant localization of gangliosides and ceramides species to A\u03b2 positive plaques, which was accompanied by distinct local reduction of sulfatides. These plaque-associated changes in sphingolipid levels implicate a functional role of sphingolipid metabolism in A\u03b2 plaque pathology and AD pathogenesis. Taken together, the presented data highlight the potential of imaging mass spectrometry as a powerful approach for probing A\u03b2 plaque-associated lipid changes underlying AD pathology.", "doi": "10.1021/acschemneuro.6b00391", "pmid": "27984697", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC5314428"}], "notes": [], "created": "2020-01-23T16:35:04.780Z", "modified": "2021-06-21T15:43:06.156Z"}, {"entity": "publication", "iuid": "b54e6c84ea604ad7899f70562f2846d1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b54e6c84ea604ad7899f70562f2846d1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b54e6c84ea604ad7899f70562f2846d1"}}, "title": "Aryl Sulfonamide Inhibitors of Insulin-Regulated Aminopeptidase Enhance Spine Density in Primary Hippocampal Neuron Cultures.", "authors": [{"family": "Diwakarla", "given": "Shanti", "initials": "S"}, {"family": "Nylander", "given": "Erik", "initials": "E"}, {"family": "Gr\u00f6nbladh", "given": "Alfhild", "initials": "A"}, {"family": "Vanga", "given": "Sudarsana Reddy", "initials": "SR"}, {"family": "Khan", "given": "Yasmin Shamsudin", "initials": "YS"}, {"family": "Guti\u00e9rrez-de-Ter\u00e1n", "given": "Hugo", "initials": "H"}, {"family": "S\u00e4vmarker", "given": "Jonas", "initials": "J"}, {"family": "Ng", "given": "Leelee", "initials": "L"}, {"family": "Pham", "given": "Vi", "initials": "V"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T"}, {"family": "Jenmalm-Jensen", "given": "Annika", "initials": "A"}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Artursson", "given": "Per", "initials": "P"}, {"family": "Zelleroth", "given": "Sofia", "initials": "S"}, {"family": "Engen", "given": "Karin", "initials": "K"}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U"}, {"family": "Larhed", "given": "Mats", "initials": "M"}, {"family": "\u00c5qvist", "given": "Johan", "initials": "J", "orcid": "0000-0003-2091-0610", "researcher": {"href": "https://publications.scilifelab.se/researcher/9777a1c6e1bd4181bc46dce4be3c2146.json"}}, {"family": "Chai", "given": "Siew Yeen", "initials": "SY"}, {"family": "Hallberg", "given": "Mathias", "initials": "M"}], "type": "journal article", "published": "2016-10-19", "journal": {"volume": "7", "issn": "1948-7193", "issue": "10", "pages": "1383-1392", "title": "ACS Chem Neurosci", "issn-l": "1948-7193"}, "abstract": "The zinc metallopeptidase insulin regulated aminopeptidase (IRAP), which is highly expressed in the hippocampus and other brain regions associated with cognitive function, has been identified as a high-affinity binding site of the hexapeptide angiotensin IV (Ang IV). This hexapeptide is thought to facilitate learning and memory by binding to the catalytic site of IRAP to inhibit its enzymatic activity. In support of this hypothesis, low molecular weight, nonpeptide specific inhibitors of IRAP have been shown to enhance memory in rodent models. Recently, it was demonstrated that linear and macrocyclic Ang IV-derived peptides can alter the shape and increase the number of dendritic spines in hippocampal cultures, properties associated with enhanced cognitive performance. After screening a library of 10\u202f500 drug-like substances for their ability to inhibit IRAP, we identified a series of low molecular weight aryl sulfonamides, which exhibit no structural similarity to Ang IV, as moderately potent IRAP inhibitors. A structural and biological characterization of three of these aryl sulfonamides was performed. Their binding modes to human IRAP were explored by docking calculations combined with molecular dynamics simulations and binding affinity estimations using the linear interaction energy method. Two alternative binding modes emerged from this analysis, both of which correctly rank the ligands according to their experimental binding affinities for this series of compounds. Finally, we show that two of these drug-like IRAP inhibitors can alter dendritic spine morphology and increase spine density in primary cultures of hippocampal neurons.", "doi": "10.1021/acschemneuro.6b00146", "pmid": "27501164", "labels": {"Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Collaborative"}, "xrefs": [], "notes": "Laboratories for Chemical Biology at Karolinska Institutet (LCBKI)\nUppsala Drug Optimization and Pharmaceutical Profiling (UDOPP)\nADME of Therapeutics (UDOPP)", "created": "2017-05-08T07:56:28.345Z", "modified": "2025-10-17T13:05:09.152Z"}], "created": "2017-05-09T09:12:18.685Z", "modified": "2020-11-27T13:14:08.460Z"}