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Identification of e...
Identification of early neurodegenerative pathways in progressive multiple sclerosis
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Kaufmann, M. (author)
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Schaupp, A. -L (author)
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Sun, R. (author)
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Coscia, F. (author)
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Dendrou, C. A. (author)
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Cortes, A. (author)
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Kaur, G. (author)
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Evans, H. G. (author)
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- Mollbrink, Annelie (author)
- KTH,Science for Life Laboratory, SciLifeLab,Genteknologi
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- Fernandez Navarro, Jose (author)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
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Sonner, J. K. (author)
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Mayer, C. (author)
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DeLuca, G. C. (author)
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- Lundeberg, Joakim (author)
- KTH,Science for Life Laboratory, SciLifeLab,Genteknologi
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Matthews, P. M. (author)
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Attfield, K. E. (author)
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Friese, M. A. (author)
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Mann, M. (author)
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Fugger, L. (author)
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(creator_code:org_t)
- 2022-06-20
- 2022
- English.
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In: Nature Neuroscience. - : Springer Nature. - 1097-6256 .- 1546-1726. ; 25:7, s. 944-955
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- proteome
- transcriptome
- animal experiment
- animal model
- antiinflammatory activity
- Article
- brain tissue
- cell communication
- cell interaction
- central nervous system disease
- cohort analysis
- controlled study
- degenerative disease
- deterioration
- disease course
- disease model
- drug targeting
- female
- gene knockdown
- human
- human tissue
- in vivo study
- male
- microenvironment
- mouse
- multiple sclerosis
- nerve cell
- nerve degeneration
- nonhuman
- pathogenesis
- protein interaction
- proteomics
- spatial analysis
- transcriptomics
- complication
- disease exacerbation
- metabolism
- pathology
- Central Nervous System Diseases
- Disease Progression
- Humans
- Neurons
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Kaufmann, M.
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Schaupp, A. -L
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Sun, R.
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Coscia, F.
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Dendrou, C. A.
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Cortes, A.
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show more...
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Kaur, G.
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Evans, H. G.
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Mollbrink, Annel ...
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Fernandez Navarr ...
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Sonner, J. K.
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Mayer, C.
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DeLuca, G. C.
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Lundeberg, Joaki ...
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Matthews, P. M.
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Attfield, K. E.
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Friese, M. A.
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Mann, M.
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Fugger, L.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Nature Neuroscie ...
- By the university
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Royal Institute of Technology