As a Potential Therapeutic Target, C1q Induces Synapse Loss Via Inflammasome-activating Apoptotic and Mitochondria Impairment Mechanisms in Alzheimer’s Disease

Guan, Peipei; Ge, Tingting; Wang, Pu

doi:10.1007/s11481-023-10076-9

Cited by 5 publications

(3 citation statements)

References 130 publications

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“…This simultaneous change in synaptic alteration and mitochondrial dysfunction is noted across various neurodegenerative conditions, AD included . Activation of classical complement pathway impairs mitochondria, which caused microglia to phagocytose synapses . Our in vivo results demonstrated that TW-7 regulates mitochondrial function by targeting C1q to make synapses not “weak”, thereby reducing microglia phagocytose of synapses.…”

Section: Resultsmentioning

confidence: 56%

Walnut-Derived Peptides Alleviate Learning and Memory Impairments in a Mice Model via Inhibition of Microglia Phagocytose Synapses

Xing,

Shi,

Gao

et al. 2024

J. Agric. Food Chem.

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Section: Resultsmentioning

confidence: 56%

Walnut-Derived Peptides Alleviate Learning and Memory Impairments in a Mice Model via Inhibition of Microglia Phagocytose Synapses

Xing,

Shi,

Gao

et al. 2024

J. Agric. Food Chem.

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“…Numerous studies underscore mitochondrial dysfunction as a significant contributor to AD pathogenesis. For example, it has been observed that Aβ infiltration into mitochondria disrupts energy production at synapses, impeding neuron communication and resulting in cognitive decline [ 3 ]. Additionally, Aβ was demonstrated to interact with dynamin-related protein 1/DRP1, a mitochondrial protein responsible for mitochondrial fission.…”

Section: Interplay Of Complement and Mitochondria In Human Diseasesmentioning

confidence: 99%

“…Hence known as the powerhouse of the cell, mitochondrial dysfunction can lead to severe consequences. Impaired mitochondria have a causal relationship with several diseases, such as neurodegenerative disorders, metabolic syndromes, and cardiovascular diseases [ 1 , 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Double-Edged Sword: Exploring the Mitochondria–Complement Bidirectional Connection in Cellular Response and Disease

Lin,

Hwang,

Luo

et al. 2024

Biology

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Mitochondria serve an ultimate purpose that seeks to balance the life and death of cells, a role that extends well beyond the tissue and organ systems to impact not only normal physiology but also the pathogenesis of diverse diseases. Theorized to have originated from ancient proto-bacteria, mitochondria share similarities with bacterial cells, including their own circular DNA, double-membrane structures, and fission dynamics. It is no surprise, then, that mitochondria interact with a bacterium-targeting immune pathway known as a complement system. The complement system is an ancient and sophisticated arm of the immune response that serves as the body’s first line of defense against microbial invaders. It operates through a complex cascade of protein activations, rapidly identifying and neutralizing pathogens, and even aiding in the clearance of damaged cells and immune complexes. This dynamic system, intertwining innate and adaptive immunity, holds secrets to understanding numerous diseases. In this review, we explore the bidirectional interplay between mitochondrial dysfunction and the complement system through the release of mitochondrial damage-associated molecular patterns. Additionally, we explore several mitochondria- and complement-related diseases and the potential for new therapeutic strategies.

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NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma

Yin,

Song,

et al. 2024

Cancer Immunol Immunother

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The anti-tumor immune response is greatly hindered by the protumor polarization of tumor-associated macrophages (TAMs). Cancer-related inflammation plays a central role in TAMs protumor polarization. Our study explored the unique positive feedback loop between inflammasome and complement in TAMs. The present study identified NOD-like receptors family pyrin domain containing 12 (NLRP12) formed positive feedback with C1qA and drove TAMs protumor polarization via the LILRB4/NF-κB pathway. In addition, NLRP12 was predominantly expressed in TAMs and was associated with poorer prognosis in lung adenocarcinoma (LUAD) patients. Knocking down LILRB4 inhibited TAMs protumor polarization. NLRP12-overexpressing TAMs promoted tumor cells’ malignant progression and inhibited T cells’ proliferation and cytotoxic function. Lastly, NLRP12 knockout (NLRP12 −/− ) reversed macrophage polarization, enhanced T-cell anti-tumor immunity, and suppressed tumor growth. Our findings highlighted the essential role of NLRP12/C1qA positive feedback loop and the LILRB4/NF-κB pathway in promoting TAMs protumor polarization. Inhibition of NLRP12 suppressed tumor development and promoted immune response. NLRP12 may be a promising target for LUAD immunotherapy. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-024-03880-6.

show abstract

As a Potential Therapeutic Target, C1q Induces Synapse Loss Via Inflammasome-activating Apoptotic and Mitochondria Impairment Mechanisms in Alzheimer’s Disease

Cited by 5 publications

References 130 publications

Walnut-Derived Peptides Alleviate Learning and Memory Impairments in a Mice Model via Inhibition of Microglia Phagocytose Synapses

Walnut-Derived Peptides Alleviate Learning and Memory Impairments in a Mice Model via Inhibition of Microglia Phagocytose Synapses

Double-Edged Sword: Exploring the Mitochondria–Complement Bidirectional Connection in Cellular Response and Disease

NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma

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