Journal Article

DZNE-2023-00012

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Inflammation promotes synucleinopathy propagation.

Kim, T.-K. ; Bae, E.-J.Extern* ; Jung, B. C. ; Choi, M. ; Shin, S. J. ; Park, S. J. ; Kim, J. T. ; Jung, M. K. ; Ulusoy, A.DZNE* ; Song, M.-Y. ; Lee, J. S. ; Lee, H.-J. ; Di Monte, D. A.DZNE* ; Lee, S.-J. (Corresponding author)

2022
Soc. Seoul

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Please use a persistent id in citations: doi:10.1038/s12276-022-00895-w

Abstract: The clinical progression of neurodegenerative diseases correlates with the spread of proteinopathy in the brain. The current understanding of the mechanism of proteinopathy spread is far from complete. Here, we propose that inflammation is fundamental to proteinopathy spread. A sequence variant of α-synuclein (V40G) was much less capable of fibril formation than wild-type α-synuclein (WT-syn) and, when mixed with WT-syn, interfered with its fibrillation. However, when V40G was injected intracerebrally into mice, it induced aggregate spreading even more effectively than WT-syn. Aggregate spreading was preceded by sustained microgliosis and inflammatory responses, which were more robust with V40G than with WT-syn. Oral administration of an anti-inflammatory agent suppressed aggregate spreading, inflammation, and behavioral deficits in mice. Furthermore, exposure of cells to inflammatory cytokines increased the cell-to-cell propagation of α-synuclein. These results suggest that the inflammatory microenvironment is the major driver of the spread of synucleinopathy in the brain.

Keyword(s): Mice (MeSH) ; Animals (MeSH) ; alpha-Synuclein: genetics (MeSH) ; alpha-Synuclein: metabolism (MeSH) ; Synucleinopathies (MeSH) ; Brain: metabolism (MeSH) ; Neurodegenerative Diseases (MeSH) ; Inflammation (MeSH) ; Disease Models, Animal (MeSH) ; alpha-Synuclein

Note: ISSN 2092-6413 not unique: **2 hits**.

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Contributing Institute(s):

1. Neurodegeneration and Neuroprotection in Parkinson´s Disease (AG Di Monte)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2022

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; IF >= 10 ; JCR ; SCOPUS ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) Kim, T.-K. ; Bae, E.-J. ; Jung, B. C. ; Choi, M. ; Shin, S. J. ; Park, S. J. ; Kim, J. T. ; Jung, M. K. ; Ulusoy, A.DZNE* ; Song, M.-Y. ; Lee, J. S. ; Lee, H.-J. ; Di Monte, D. A.DZNE* ; Lee, S.-J.
Correction: Inflammation promotes synucleinopathy propagation
Experimental & molecular medicine 56(4), 1029 - 1030 (2024) [10.1038/s12276-024-01217-y]2024   Files  Fulltext by Pubmed Central BibTeX | EndNote: XML, Text | RIS

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