TY  - JOUR
AU  - Kim, Tae-Kyung
AU  - Bae, Eun-Jin
AU  - Jung, Byung Chul
AU  - Choi, Minsun
AU  - Shin, Soo Jean
AU  - Park, Sung Jun
AU  - Kim, Jeong Tae
AU  - Jung, Min Kyo
AU  - Ulusoy, Ayse
AU  - Song, Mi-Young
AU  - Lee, Jun Sung
AU  - Lee, He-Jin
AU  - Di Monte, Donato A
AU  - Lee, Seung-Jae
TI  - Inflammation promotes synucleinopathy propagation.
JO  - Experimental & molecular medicine
VL  - 54
IS  - 12
SN  - 2092-6413
CY  - Seoul
PB  - Soc.
M1  - DZNE-2023-00012
SP  - 2148-2161
PY  - 2022
N1  - ISSN 2092-6413 not unique: **2 hits**.
AB  - 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.
KW  - Mice
KW  - Animals
KW  - alpha-Synuclein: genetics
KW  - alpha-Synuclein: metabolism
KW  - Synucleinopathies
KW  - Brain: metabolism
KW  - Neurodegenerative Diseases
KW  - Inflammation
KW  - Disease Models, Animal
KW  - alpha-Synuclein (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC9794777
C6  - pmid:36473937
DO  - DOI:10.1038/s12276-022-00895-w
UR  - https://pub.dzne.de/record/169133
ER  -