The interaction between microglial dysfunction and mitochondrial impairment in Alzheimer’s disease DOI Creative Commons

Qiudan Luo,

Ji Heon Noh, Jian Sima

et al.

Aging Research, Journal Year: 2023, Volume and Issue: 1(2), P. 9340020 - 9340020

Published: Dec. 1, 2023

Alzheimer's disease (AD), a prevalent form of dementia in the elderly, is characterized by marked neurodegeneration and cognitive decline. Central to its pathology are Amyloid-beta plaques, neurofibrillary tangles, neuroinflammation. This review delves into pivotal role microglia, primary immune cells central nervous system, AD's progression. We highlight recent discoveries revealing how abnormal microglial activity, influenced mitochondrial dysfunction, contributes AD development. Special attention given bidirectional relationship between microglia mitochondria, including impact metabolic disturbances energy dysregulation on function. Further, we explore mechanisms underlying activation consequences neuronal health, interplay inflammatory pathways dynamics. Our comprehensive analysis underscores significance homeostasis functionality implications for progression, offering insights potential therapeutic avenues targeting mitochondria AD.

Language: Английский

Biomimetic Self‐Propelled Asymmetric Nanomotors for Cascade‐Targeted Treatment of Neurological Inflammation DOI Creative Commons
Jiamin Ye,

Yueyue Fan,

Yaoguang She

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(22)

Published: March 9, 2024

Abstract The precise targeted delivery of therapeutic agents to deep regions the brain is crucial for effective treatment various neurological diseases. However, achieving this goal challenging due presence blood‒brain barrier (BBB) and complex anatomy brain. Here, a biomimetic self‐propelled nanomotor with cascade targeting capacity developed inflammatory nanomotors are designed asymmetric structures mesoporous SiO 2 head multiple MnO tentacles. Macrophage membrane modification endows BBB penetration abilities catalyze degradation H O into , not only by reducing inflammation but also providing driving force penetration. Additionally, loaded curcumin, which actively regulates macrophage polarization from M1 M2 phenotype. All in vitro cell, organoid model, vivo animal experiments confirmed effectiveness targeting, penetration, anti‐inflammatory, nervous system function maintenance. Therefore, study introduces platform ability active

Language: Английский

Citations

34
Advanced Nanoparticle Engineering for Precision Therapeutics of Brain Diseases DOI
Muhammad Ismail, Jiayi Liu,

Ningyang Wang

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 318, P. 123138 - 123138

Published: Jan. 28, 2025

Language: Английский

Citations

2
Astragaloside IV promotes cerebral tissue restoration through activating AMPK- mediated microglia polarization in ischemic stroke rats DOI

Mingcong Li,

Jing-ting Jia,

Y Wang

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 334, P. 118532 - 118532

Published: July 6, 2024

Language: Английский

Citations

9
Mitochondrial Transplantation via Magnetically Responsive Artificial Cells Promotes Intracerebral Hemorrhage Recovery by Supporting Microglia Immunological Homeostasis DOI Creative Commons

Mi Zhou,

J. Zang,

Yuxuan Qian

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract The immune‐inflammatory responses in the brain represent a key therapeutic target to ameliorate injury following intracerebral hemorrhage (ICH), where pro‐inflammatory microglia and its mitochondrial dysfunction plays pivotal role. Mitochondrial transplantation is promising strategy improve cellular function thus modulate their immune properties. However, of naked mitochondria into has been constrained by peripheral clearance difficulty achieving selective access brain. Here, novel for via intravenous injection magnetically responsive artificial cells (ACs) are proposed. ACs can protect loaded selectively accumulate around lesion under an external magnetic field (EMF). In this study, released from effectively microglial function, attenuate attributes, elevate proportion immunosuppressive microglia. way, homeostasis reestablished, inflammation attenuated, ultimately promoting functional recovery. This study presents effective approach transplant brain, offering alternative cascade ICH.

Language: Английский

Citations

1
Decoding microglial immunometabolism: a new frontier in Alzheimer's disease research DOI Creative Commons
Eun Sun Jung, Hayoung Choi, Inhee Mook‐Jung

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 27, 2025

Abstract Alzheimer’s disease (AD) involves a dynamic interaction between neuroinflammation and metabolic dysregulation, where microglia play central role. These immune cells undergo reprogramming in response to AD-related pathology, with key genes such as TREM2, APOE, HIF-1α orchestrating these processes. Microglial metabolism adapts environmental stimuli, shifting oxidative phosphorylation glycolysis. Hexokinase-2 facilitates glycolytic flux, while AMPK acts an energy sensor, coordinating lipid glucose metabolism. TREM2 APOE regulate microglial homeostasis, influencing Aβ clearance responses. LPL ABCA7, both associated AD risk, modulate processing cholesterol transport, linking neurodegeneration. PPARG further supports by regulating inflammatory Amino acid also contributes function. Indoleamine 2,3-dioxygenase controls the kynurenine pathway, producing neurotoxic metabolites linked pathology. Additionally, glucose-6-phosphate dehydrogenase regulates pentose phosphate maintaining redox balance activation. Dysregulated metabolism, influenced genetic variants APOE4, impair responses exacerbate progression. Recent findings highlight interplay regulators like REV-ERBα, which modulates inflammation, Syk, influences clearance. insights offer promising therapeutic targets, including strategies aimed at modulation, could restore function depending on stage. By integrating metabolic, immune, factors, this review underscores importance of immunometabolism AD. Targeting pathways provide novel for mitigating restoring function, ultimately paving way innovative treatments neurodegenerative diseases.

Language: Английский

Citations

1
Highly BBB-permeable nanomedicine reverses neuroapoptosis and neuroinflammation to treat Alzheimer's disease DOI

Aihua Xie,

Guowang Cheng,

Jiaxin Wu

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 312, P. 122749 - 122749

Published: Aug. 6, 2024

Language: Английский

Citations

7
Intranasal Delivery of Pure Nanodrug Loaded Liposomes for Alzheimer's Disease Treatment by Efficiently Regulating Microglial Polarization DOI Open Access
Qianhua Feng, Xueli Zhang, Xiaowen Zhao

et al.

Small, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 6, 2024

Abstract The activated M1‐like microglia induced neuroinflammation is the critical pathogenic event in Alzheimer's disease (AD). Microglial polarization from pro‐inflammatory M1 toward anti‐inflammatory M2 phenotype a promising strategy. To efficiently accomplish this, amyloid‐β (Aβ) aggregates as culprit of activation should be uprooted. Interestingly, this study finds out that self‐reassembly curcumin molecules into carrier‐free nanoparticles (CNPs) exhibits multivalent binding with Aβ to achieve higher inhibitory effect on aggregation, compared free monovalent effect. Based CNPs loaded cardiolipin liposomes are developed for efficient microglial polarization. After intranasal administration, decompose release and response AD oxidative microenvironment. inhibit aggregation promote phagocytosis/clearance microglia, removing roadblock Subsequently, endocytosed by TLR4/NF‐κB pathway (M1→M2). Meanwhile, identified signaling molecule normalize dysfunction prevent factors release. In transgenic mice, neuroinflammation, burden, memory deficits relieved after treatment. Through combined attack extracellularly eradicating intracellularly inhibiting inflammation‐related pathways, nanotechnology assisted delivery system polarizes efficiently, providing reliable strategy

Language: Английский

Citations

7
Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization DOI Creative Commons
Qi Wang, Jiaxin Dong, Mengxian Du

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 2265 - 2284

Published: March 1, 2024

Introduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment.Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder potential clinical applications.Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization CS RAPA transmission electron microscopy, Fourier transform infrared spectra, proton nuclear magnetic resonance.In vitro assays on human umbilical cord vein endothelial rat cell line examined biocompatibility anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) measured effects microglial polarization.In vivo, using mouse ischemia/reperfusion (I/R) model acute intraocular pressure elevation, the CRCD visual function, apoptosis, oxidative stress, M2 polarization were examined.Results: exhibited good solubility form free radical scavenging.In vitro, bio-compatible lowered which also found vivo I/R model.Additionally, both BV2 model, able promote activating autophagy, which, turn, down-regulated pro-inflammatory cytokines, such as IL-1β TNF-α, well up-regulated anti-inflammatory IL-4 TGF-β.All these ultimately aided preserving RGCs, subsequently, improved function.Discussion: could serve novel treatment strategy for glaucoma, incorporating into CDs, turn not only mitigating toxic side enhancing therapeutic efficacy.

Language: Английский

Citations

5
Glycolytic dysregulation in Alzheimer’s disease: unveiling new avenues for understanding pathogenesis and improving therapy DOI Creative Commons
You Wu, Lijie Yang,

Wanrong Jiang

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(8), P. 2264 - 2278

Published: July 29, 2024

Alzheimer’s disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence curative treatments. The current therapeutic strategies, primarily based on cholinesterase inhibitors N-methyl-D-aspartate receptor antagonists, offer limited symptomatic relief without halting progression, highlighting an urgent need for novel research directions that address key mechanisms underlying disease. Recent studies have provided insights into critical role glycolysis, fundamental energy metabolism pathway in brain, pathogenesis Alterations glycolytic processes within neurons glial cells, including microglia, astrocytes, oligodendrocytes, been identified as contributors pathological landscape Glycolytic changes impact neuronal function, thus offering promising targets intervention. purpose this review is consolidate knowledge modifications glycolysis associated with explore by which these abnormalities contribute onset progression. Comprehensive focus pathways through dysfunction influences pathology should provide potential strategies pave way groundbreaking treatments, emphasizing importance understanding metabolic quest clarification management

Language: Английский

Citations

4
Anti‐Tumor Strategies Targeting Nutritional Deprivation: Challenges and Opportunities DOI Open Access
Jinsheng Shi, Wei Han, Jie Wang

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Higher and richer nutrient requirements are typical features that distinguish tumor cells from AU: cells, ensuring adequate substrates energy sources for cell proliferation migration. Therefore, deprivation strategies based on targeted technologies can induce impaired viability in which more sensitive than normal cells. In this review, nutrients required by related metabolic pathways introduced, anti-tumor developed to target described. addition the nutritional characteristics of other microenvironment (including macrophages, neutrophils, natural killer T cancer-associated fibroblasts) new also summarized. conclusion, recent advances targeting blockade reviewed, challenges prospects these discussed, theoretical significance optimizing clinical application nutrition strategies.

Language: Английский

Citations

0