Microglial cGAS Deletion Preserves Intercellular Communication and Alleviates Amyloid‐β‐Induced Pathogenesis of Alzheimer's Disease DOI Creative Commons
Sijia He, Xin Li,

Namrata Mittra

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract Innate immune activation plays a crucial role in the pathogenesis of Alzheimer's disease (AD) and related dementias (ADRD). The cytosolic DNA sensing pathway, involving cGAMP synthase (cGAS) Stimulator Interferon Genes (STING), has emerged as key mediator neurodegenerative diseases. However, precise mechanisms through which cGAS influences AD progression remain poorly understood. In this study, we observed significant up‐regulation cGAS‐STING signaling pathway AD. Notably, increase is primarily attributed to microglia, rather than non‐microglial cell types. Using an inducible, microglia‐specific knockout mouse model 5xFAD background, demonstrated that deleting microglial at onset amyloid‐β (Aβ) pathology profoundly restricts plaque accumulation protects mice from Aβ‐induced cognitive impairment. Mechanistically, our study revealed promotes plaque‐associated microglia essential for inflammasome activation. Moreover, showed restricting cGAS‐mediated innate immunity preserving inter‐cellular communication brain induces pleiotrophin, neuroprotective factor. These findings offer novel insights into specific roles system employing cell‐type‐specific approach. conclusions provide foundation targeted interventions modulate offering promising therapeutic strategy treatment.

Язык: Английский

Lipidome disruption in Alzheimer’s disease brain: detection, pathological mechanisms, and therapeutic implications DOI Creative Commons
Sijia He, Ziying Xu, Xianlin Han

и другие.

Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 27, 2025

Alzheimer's disease (AD) is among the most devastating neurodegenerative disorders with limited treatment options. Emerging evidence points to involvement of lipid dysregulation in development AD. Nevertheless, precise lipidomic landscape and mechanistic roles lipids pathology remain poorly understood. This review aims highlight significance lipidomics lipid-targeting approaches diagnosis We summarized connection between human brain AD at both genetic species levels. briefly introduced technologies discussed potential challenges areas future advancements field for research. To elucidate central role converging multiple pathological aspects AD, we reviewed current knowledge on interplay major features, including amyloid beta, tau, neuroinflammation. Finally, assessed progresses obstacles lipid-based therapeutics proposed strategies leveraging

Язык: Английский

Процитировано

2
Microglial cGAS Deletion Preserves Intercellular Communication and Alleviates Amyloid‐β‐Induced Pathogenesis of Alzheimer's Disease DOI Creative Commons
Sijia He, Xin Li,

Namrata Mittra

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract Innate immune activation plays a crucial role in the pathogenesis of Alzheimer's disease (AD) and related dementias (ADRD). The cytosolic DNA sensing pathway, involving cGAMP synthase (cGAS) Stimulator Interferon Genes (STING), has emerged as key mediator neurodegenerative diseases. However, precise mechanisms through which cGAS influences AD progression remain poorly understood. In this study, we observed significant up‐regulation cGAS‐STING signaling pathway AD. Notably, increase is primarily attributed to microglia, rather than non‐microglial cell types. Using an inducible, microglia‐specific knockout mouse model 5xFAD background, demonstrated that deleting microglial at onset amyloid‐β (Aβ) pathology profoundly restricts plaque accumulation protects mice from Aβ‐induced cognitive impairment. Mechanistically, our study revealed promotes plaque‐associated microglia essential for inflammasome activation. Moreover, showed restricting cGAS‐mediated innate immunity preserving inter‐cellular communication brain induces pleiotrophin, neuroprotective factor. These findings offer novel insights into specific roles system employing cell‐type‐specific approach. conclusions provide foundation targeted interventions modulate offering promising therapeutic strategy treatment.

Язык: Английский

Процитировано

1