Identification of early neurodegenerative pathways in progressive multiple sclerosis

Research output: Contribution to journal › Journal article › Research › peer-review

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Identification of early neurodegenerative pathways in progressive multiple sclerosis. / Kaufmann, Max; Schaupp, Anna Lena; Sun, Rosa; Coscia, Fabian; Dendrou, Calliope A.; Cortes, Adrian; Kaur, Gurman; Evans, Hayley G.; Mollbrink, Annelie; Navarro, José Fernández; Sonner, Jana K.; Mayer, Christina; DeLuca, Gabriele C.; Lundeberg, Joakim; Matthews, Paul M.; Attfield, Kathrine E.; Friese, Manuel A.; Mann, Matthias; Fugger, Lars.

In: Nature Neuroscience, Vol. 25, 2022, p. 944-955.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kaufmann, M, Schaupp, AL, Sun, R, Coscia, F, Dendrou, CA, Cortes, A, Kaur, G, Evans, HG, Mollbrink, A, Navarro, JF, Sonner, JK, Mayer, C, DeLuca, GC, Lundeberg, J, Matthews, PM, Attfield, KE, Friese, MA, Mann, M & Fugger, L 2022, 'Identification of early neurodegenerative pathways in progressive multiple sclerosis', Nature Neuroscience, vol. 25, pp. 944-955. https://doi.org/10.1038/s41593-022-01097-3

APA

Kaufmann, M., Schaupp, A. L., Sun, R., Coscia, F., Dendrou, C. A., Cortes, A., Kaur, G., Evans, H. G., Mollbrink, A., Navarro, J. F., Sonner, J. K., Mayer, C., DeLuca, G. C., Lundeberg, J., Matthews, P. M., Attfield, K. E., Friese, M. A., Mann, M., & Fugger, L. (2022). Identification of early neurodegenerative pathways in progressive multiple sclerosis. Nature Neuroscience, 25, 944-955. https://doi.org/10.1038/s41593-022-01097-3

Vancouver

Kaufmann M, Schaupp AL, Sun R, Coscia F, Dendrou CA, Cortes A et al. Identification of early neurodegenerative pathways in progressive multiple sclerosis. Nature Neuroscience. 2022;25:944-955. https://doi.org/10.1038/s41593-022-01097-3

Author

Kaufmann, Max ; Schaupp, Anna Lena ; Sun, Rosa ; Coscia, Fabian ; Dendrou, Calliope A. ; Cortes, Adrian ; Kaur, Gurman ; Evans, Hayley G. ; Mollbrink, Annelie ; Navarro, José Fernández ; Sonner, Jana K. ; Mayer, Christina ; DeLuca, Gabriele C. ; Lundeberg, Joakim ; Matthews, Paul M. ; Attfield, Kathrine E. ; Friese, Manuel A. ; Mann, Matthias ; Fugger, Lars. / Identification of early neurodegenerative pathways in progressive multiple sclerosis. In: Nature Neuroscience. 2022 ; Vol. 25. pp. 944-955.

Bibtex

@article{a651cdb5e5884cd286a505e67cd55c72,
title = "Identification of early neurodegenerative pathways in progressive multiple sclerosis",
abstract = "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.",
author = "Max Kaufmann and Schaupp, {Anna Lena} and Rosa Sun and Fabian Coscia and Dendrou, {Calliope A.} and Adrian Cortes and Gurman Kaur and Evans, {Hayley G.} and Annelie Mollbrink and Navarro, {Jos{\'e} Fern{\'a}ndez} and Sonner, {Jana K.} and Christina Mayer and DeLuca, {Gabriele C.} and Joakim Lundeberg and Matthews, {Paul M.} and Attfield, {Kathrine E.} and Friese, {Manuel A.} and Matthias Mann and Lars Fugger",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
doi = "10.1038/s41593-022-01097-3",
language = "English",
volume = "25",
pages = "944--955",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Identification of early neurodegenerative pathways in progressive multiple sclerosis

AU - Kaufmann, Max

AU - Schaupp, Anna Lena

AU - Sun, Rosa

AU - Coscia, Fabian

AU - Dendrou, Calliope A.

AU - Cortes, Adrian

AU - Kaur, Gurman

AU - Evans, Hayley G.

AU - Mollbrink, Annelie

AU - Navarro, José Fernández

AU - Sonner, Jana K.

AU - Mayer, Christina

AU - DeLuca, Gabriele C.

AU - Lundeberg, Joakim

AU - Matthews, Paul M.

AU - Attfield, Kathrine E.

AU - Friese, Manuel A.

AU - Mann, Matthias

AU - Fugger, Lars

N1 - Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1038/s41593-022-01097-3

DO - 10.1038/s41593-022-01097-3

M3 - Journal article

C2 - 35726057

AN - SCOPUS:85132570612

VL - 25

SP - 944

EP - 955

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

ER -

ID: 312697589