FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4380204080> ?p ?o ?g. }

• W4380204080 endingPage "2284" @default.
• W4380204080 startingPage "2266" @default.
• W4380204080 abstract "Synucleinopathies refer to a range of neurodegenerative diseases caused by abnormal α-synuclein (α-Syn) deposition, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Their pathogenesis is strongly linked to microglial dysfunction and neuroinflammation, which involves the leucine-rich-repeat kinase 2 (LRRK2)-regulated nuclear factor of activated T-cells (NFAT). Of the NFAT family, NFATc1 has been found to be increasingly translocated into the nucleus in α-syn stimulation. However, the specific role of NFATc1-mediated intracellular signaling in PD remains elusive in regulating microglial functions. In the current study, we crossbred LRRK2 or NFATc1 conditional knockout mice with Lyz2Cre mice to generate mice with microglia-specific deletion of LRRK2 or NFATc1, and by stereotactic injection of fibrillary α-Syn, we generated PD models in these mice. We found that LRRK2 deficiency enhanced microglial phagocytosis in the mice after α-Syn exposure and that genetic inhibition of NFATc1 markedly diminished phagocytosis and α-Syn elimination. We further demonstrated that LRRK2 negatively regulated NFATc1 in α-Syn-treated microglia, in which microglial LRRK2-deficiency facilitated NFATc1 nuclear translocation, CX3CR1 upregulation, and microglia migration. Additionally, NFATc1 translocation upregulated the expression of Rab7 and promoted the formation of late lysosomes, resulting in α-Syn degradation. In contrast, the microglial NFATc1 deficiency impaired CX3CR1 upregulation and the formation of Rab7-mediated late lysosomes. These findings highlight the critical role of NFATc1 in modulating microglial migration and phagocytosis, in which the LRRK2-NFATc1 signaling pathway regulates the expression of microglial CX3CR1 and endocytic degradative Rab7 to attenuate α-synuclein immunotoxicity." @default.
• W4380204080 created "2023-06-11" @default.
• W4380204080 creator A5001582203 @default.
• W4380204080 creator A5006656608 @default.
• W4380204080 creator A5018974469 @default.
• W4380204080 creator A5022708768 @default.
• W4380204080 creator A5028200481 @default.
• W4380204080 creator A5041104900 @default.
• W4380204080 creator A5067409432 @default.
• W4380204080 creator A5084202563 @default.
• W4380204080 date "2023-06-10" @default.
• W4380204080 modified "2023-10-18" @default.
• W4380204080 title "Microglial <scp>LRRK2</scp>‐mediated <scp>NFATc1</scp> attenuates α‐synuclein immunotoxicity in association with <scp>CX3CR1</scp>‐induced migration and the lysosome‐initiated degradation" @default.
• W4380204080 cites W1921896771 @default.
• W4380204080 cites W1963664876 @default.
• W4380204080 cites W1974966491 @default.
• W4380204080 cites W1977267085 @default.
• W4380204080 cites W1978467560 @default.
• W4380204080 cites W1992365739 @default.
• W4380204080 cites W1996055705 @default.
• W4380204080 cites W1999553835 @default.
• W4380204080 cites W2008554402 @default.
• W4380204080 cites W2011331018 @default.
• W4380204080 cites W2020831499 @default.
• W4380204080 cites W2021714743 @default.
• W4380204080 cites W2048256242 @default.
• W4380204080 cites W2049217614 @default.
• W4380204080 cites W2059195281 @default.
• W4380204080 cites W2065805006 @default.
• W4380204080 cites W2067267561 @default.
• W4380204080 cites W2074825064 @default.
• W4380204080 cites W2075793841 @default.
• W4380204080 cites W2086776463 @default.
• W4380204080 cites W2100894616 @default.
• W4380204080 cites W2106072892 @default.
• W4380204080 cites W2108175824 @default.
• W4380204080 cites W2113107925 @default.
• W4380204080 cites W2117667168 @default.
• W4380204080 cites W2132259121 @default.
• W4380204080 cites W2144618115 @default.
• W4380204080 cites W2154616452 @default.
• W4380204080 cites W2163487275 @default.
• W4380204080 cites W2165447336 @default.
• W4380204080 cites W2295300743 @default.
• W4380204080 cites W2439312023 @default.
• W4380204080 cites W2465699308 @default.
• W4380204080 cites W2470877775 @default.
• W4380204080 cites W2559466447 @default.
• W4380204080 cites W2591587397 @default.
• W4380204080 cites W2599239219 @default.
• W4380204080 cites W2768016303 @default.
• W4380204080 cites W2795978601 @default.
• W4380204080 cites W2800782157 @default.
• W4380204080 cites W2802496601 @default.
• W4380204080 cites W2804685648 @default.
• W4380204080 cites W2883704778 @default.
• W4380204080 cites W2885329575 @default.
• W4380204080 cites W2901838561 @default.
• W4380204080 cites W2906211657 @default.
• W4380204080 cites W2913929619 @default.
• W4380204080 cites W2951881808 @default.
• W4380204080 cites W2980464820 @default.
• W4380204080 cites W2991329979 @default.
• W4380204080 cites W3011593562 @default.
• W4380204080 cites W3027294740 @default.
• W4380204080 cites W3033231936 @default.
• W4380204080 cites W3037586787 @default.
• W4380204080 cites W3045733764 @default.
• W4380204080 cites W3092933686 @default.
• W4380204080 cites W3093442491 @default.
• W4380204080 cites W3096916956 @default.
• W4380204080 cites W3133761729 @default.
• W4380204080 cites W3196008740 @default.
• W4380204080 cites W4206915089 @default.
• W4380204080 cites W4213284669 @default.
• W4380204080 cites W4297035951 @default.
• W4380204080 cites W4307423278 @default.
• W4380204080 doi "https://doi.org/10.1002/glia.24422" @default.
• W4380204080 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37300531" @default.
• W4380204080 hasPublicationYear "2023" @default.
• W4380204080 type Work @default.
• W4380204080 citedByCount "0" @default.
• W4380204080 crossrefType "journal-article" @default.
• W4380204080 hasAuthorship W4380204080A5001582203 @default.
• W4380204080 hasAuthorship W4380204080A5006656608 @default.
• W4380204080 hasAuthorship W4380204080A5018974469 @default.
• W4380204080 hasAuthorship W4380204080A5022708768 @default.
• W4380204080 hasAuthorship W4380204080A5028200481 @default.
• W4380204080 hasAuthorship W4380204080A5041104900 @default.
• W4380204080 hasAuthorship W4380204080A5067409432 @default.
• W4380204080 hasAuthorship W4380204080A5084202563 @default.
• W4380204080 hasConcept C104317684 @default.
• W4380204080 hasConcept C127561419 @default.
• W4380204080 hasConcept C12823836 @default.
• W4380204080 hasConcept C13373296 @default.
• W4380204080 hasConcept C189938988 @default.
• W4380204080 hasConcept C203014093 @default.
• W4380204080 hasConcept C2776914184 @default.

• next