Sökning: WFRF:(Dendrou C. A.) > (2022) > Identification of e...
Fältnamn | Indikatorer | Metadata |
---|---|---|
000 | 04646naa a2201021 4500 | |
001 | oai:DiVA.org:kth-324939 | |
003 | SwePub | |
008 | 230327s2022 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-3249392 URI |
024 | 7 | a https://doi.org/10.1038/s41593-022-01097-32 DOI |
040 | a (SwePub)kth | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Kaufmann, M.4 aut |
245 | 1 0 | a Identification of early neurodegenerative pathways in progressive multiple sclerosis |
264 | c 2022-06-20 | |
264 | 1 | b Springer Nature,c 2022 |
338 | a print2 rdacarrier | |
500 | a QC 20230327 | |
520 | a Progressive multiple sclerosis (MS) is characterized by unrelenting neurodegeneration, which causes cumulative disability and is refractory to current treatments. Drug development to prevent disease progression is an urgent clinical need yet is constrained by an incomplete understanding of its complex pathogenesis. Using spatial transcriptomics and proteomics on fresh-frozen human MS brain tissue, we identified multicellular mechanisms of progressive MS pathogenesis and traced their origin in relation to spatially distributed stages of neurodegeneration. By resolving ligand–receptor interactions in local microenvironments, we discovered defunct trophic and anti-inflammatory intercellular communications within areas of early neuronal decline. Proteins associated with neuronal damage in patient samples showed mechanistic concordance with published in vivo knockdown and central nervous system (CNS) disease models, supporting their causal role and value as potential therapeutic targets in progressive MS. Our findings provide a new framework for drug development strategies, rooted in an understanding of the complex cellular and signaling dynamics in human diseased tissue that facilitate this debilitating disease. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng |
653 | a proteome | |
653 | a transcriptome | |
653 | a animal experiment | |
653 | a animal model | |
653 | a antiinflammatory activity | |
653 | a Article | |
653 | a brain tissue | |
653 | a cell communication | |
653 | a cell interaction | |
653 | a central nervous system disease | |
653 | a cohort analysis | |
653 | a controlled study | |
653 | a degenerative disease | |
653 | a deterioration | |
653 | a disease course | |
653 | a disease model | |
653 | a drug targeting | |
653 | a female | |
653 | a gene knockdown | |
653 | a human | |
653 | a human tissue | |
653 | a in vivo study | |
653 | a male | |
653 | a microenvironment | |
653 | a mouse | |
653 | a multiple sclerosis | |
653 | a nerve cell | |
653 | a nerve degeneration | |
653 | a nonhuman | |
653 | a pathogenesis | |
653 | a protein interaction | |
653 | a proteomics | |
653 | a spatial analysis | |
653 | a transcriptomics | |
653 | a complication | |
653 | a disease exacerbation | |
653 | a metabolism | |
653 | a pathology | |
653 | a Central Nervous System Diseases | |
653 | a Disease Progression | |
653 | a Humans | |
653 | a Neurons | |
700 | 1 | a Schaupp, A. -L4 aut |
700 | 1 | a Sun, R.4 aut |
700 | 1 | a Coscia, F.4 aut |
700 | 1 | a Dendrou, C. A.4 aut |
700 | 1 | a Cortes, A.4 aut |
700 | 1 | a Kaur, G.4 aut |
700 | 1 | a Evans, H. G.4 aut |
700 | 1 | a Mollbrink, Annelieu KTH,Science for Life Laboratory, SciLifeLab,Genteknologi4 aut0 (Swepub:kth)u18ttoxc |
700 | 1 | a Fernandez Navarro, Joseu KTH,Genteknologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:kth)u11gbovc |
700 | 1 | a Sonner, J. K.4 aut |
700 | 1 | a Mayer, C.4 aut |
700 | 1 | a DeLuca, G. C.4 aut |
700 | 1 | a Lundeberg, Joakimu KTH,Science for Life Laboratory, SciLifeLab,Genteknologi4 aut0 (Swepub:kth)u1qkn9kw |
700 | 1 | a Matthews, P. M.4 aut |
700 | 1 | a Attfield, K. E.4 aut |
700 | 1 | a Friese, M. A.4 aut |
700 | 1 | a Mann, M.4 aut |
700 | 1 | a Fugger, L.4 aut |
710 | 2 | a KTHb Science for Life Laboratory, SciLifeLab4 org |
773 | 0 | t Nature Neuroscienced : Springer Natureg 25:7, s. 944-955q 25:7<944-955x 1097-6256x 1546-1726 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-324939 |
856 | 4 8 | u https://doi.org/10.1038/s41593-022-01097-3 |
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