Microglia from patients with multiple sclerosis display a cell-autonomous immune activation state DOI Open Access
Tanja Hyvärinen, Johanna Lotila, Luca Giudice

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 11, 2024

Abstract Aberrant and sustained activation of microglia is implicated in the progression severity multiple sclerosis (MS). However, whether intrinsic alterations microglial function impact pathogenesis this disease remains unclear. We conducted transcriptomic functional analyses microglia-like cells (iMGLs) differentiated from induced pluripotent stem (iPSCs) patients with MS (pwMS) to answer question. generated iPSCs six pwMS showing increased activity via translocator protein (TSPO)-PET imaging. demonstrated that iMGL transcriptional profile resembled signature found lesions. Importantly, compared healthy controls, iMGLs presented cell-autonomous differences their regulation inflammation, both basal state following inflammatory lipopolysaccharide challenge. Through profiling, we showed display expression genes known be upregulated microglia. Furthermore, were associated immune receptor activation, antigen presentation, complement system, implications. Finally, indicated changes corresponded secretion cytokines chemokines phagocytosis. Together, our results provide evidence putative identify recapitulate phenotypes observed vivo pwMS. These findings indicate disease-specific are valuable tools for studying vitro highlight as potential therapeutic targets MS.

Язык: Английский

The Concept of Neuroglia ‐ the State of the Art Circa 1900 DOI Creative Commons
Helmut Kettenmann, Bilge Ugursu, Bruce R. Ransom

и другие.

Glia, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

ABSTRACT Glial cells were first defined by Rudolf Virchow in 1856. About 40 years later, glial research had developed into a field distinct from the mainstream study of neurons as central elements governing brain function. By that time, substantial knowledge about properties accumulated, exemplified five important publications four distinguished investigators: Gustav Retzius, Michael von Lenhossek, Carl Weigert, and Hans Held. These treatises broadly summarized what was known cells, comparing findings leeches to humans. Practically speaking, these articles represent foundation our current knowledge. All contributions published German, which at time one dominant languages for scientific exchange. This article summarizes comments on their thus provides insight time. More importantly, Supporting Information, we provide English translations original scans publications, making them accessible an international readership.

Язык: Английский

Процитировано

1
Targeting active microglia alleviates distal edge of proton radiation-induced neural damage DOI Creative Commons

Keman Liao,

Dan Ou,

Chen Mei

и другие.

Advances in Radiation Oncology, Год журнала: 2025, Номер unknown, С. 101764 - 101764

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Discovery of Limonoids from Xylocarpus granatum as Potential Leads against Neuroinflammation DOI
Wei Zhao,

Fulan Luo,

Li-Fu Liu

и другие.

Journal of Natural Products, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

Discovery of new natural products with both anti-inflammatory effects on activated microglia and protective activity dopaminergic neurons is a strategy to find drug leads against neuroinflammation in Parkinson's disease. In this work, nine limonoids, named thaigranatumins A-I (1-9), two protolimonoids, J (10) K (11), were obtained from seeds the Thai mangrove, Xylocarpus granatum. The structures these compounds established by analysis spectroscopic data, single-crystal X-ray diffraction (Cu Kα), comparison experimental calculated ECD spectra. Thaigranatumin A (1), containing C-16/C-30 δ-lactone ring-D tetra-substituted C8-O-C17-bridged tetrahydrofuran ring-F, first limonoid featuring unique 6/6/6/6/6/5/5-fused heptacyclic framework. G (7) exhibited inhibitory protein expression iNOS, COX2, IL-1β lipopolysaccharide-stimulated mouse BV2 cells neuroprotective rotenone-induced injury midbrain neuron MN9D dose-dependent manner. Preliminary bioassays indicated that thaigranatumin might be valuable lead neuroinflammation, thus warranting further studies.

Язык: Английский

Процитировано

0
Microglia from patients with multiple sclerosis display a cell-autonomous immune activation state DOI Open Access
Tanja Hyvärinen, Johanna Lotila, Luca Giudice

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 11, 2024

Abstract Aberrant and sustained activation of microglia is implicated in the progression severity multiple sclerosis (MS). However, whether intrinsic alterations microglial function impact pathogenesis this disease remains unclear. We conducted transcriptomic functional analyses microglia-like cells (iMGLs) differentiated from induced pluripotent stem (iPSCs) patients with MS (pwMS) to answer question. generated iPSCs six pwMS showing increased activity via translocator protein (TSPO)-PET imaging. demonstrated that iMGL transcriptional profile resembled signature found lesions. Importantly, compared healthy controls, iMGLs presented cell-autonomous differences their regulation inflammation, both basal state following inflammatory lipopolysaccharide challenge. Through profiling, we showed display expression genes known be upregulated microglia. Furthermore, were associated immune receptor activation, antigen presentation, complement system, implications. Finally, indicated changes corresponded secretion cytokines chemokines phagocytosis. Together, our results provide evidence putative identify recapitulate phenotypes observed vivo pwMS. These findings indicate disease-specific are valuable tools for studying vitro highlight as potential therapeutic targets MS.

Язык: Английский

Процитировано

0