Lipidome disruption in Alzheimer’s disease brain: detection, pathological mechanisms, and therapeutic implications

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

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The role of astrocyte metabolic reprogramming in ischemic stroke (Review)

International Journal of Molecular Medicine, Год журнала: 2025, Номер 55(3)

Опубликована: Янв. 21, 2025

Ischemic stroke, a leading cause of disability and mortality worldwide, is characterized by the sudden loss blood flow in specific area brain. Intravenous thrombolysis with recombinant tissue plasminogen activator only approved pharmacological treatment for acute ischemic stroke; however, aforementioned has significant clinical limitations, thus there an urgent need development novel mechanisms therapeutic strategies stroke. Astrocytes, abundant versatile cells central nervous system, offer crucial support to neurons nutritionally, structurally physically. They also contribute blood‑brain barrier formation regulate neuronal extracellular ion concentrations. Accumulated evidence revealed involvement astrocytes regulation host neurotransmitter metabolism, immune response repair, different metabolic characteristics can process suggesting that targeted astrocyte reprogramming may prognosis In present review, current understanding multifaceted along its regulatory factors pathways, as well promote polarization balance, which hold promise immunometabolism‑targeted therapies were summarized.

Язык: Английский

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Lipids shape brain function through ion channel and receptor modulations: physiological mechanisms and clinical perspectives

Physiological Reviews, Год журнала: 2024, Номер 105(1), С. 137 - 207

Опубликована: Июль 11, 2024

Lipids represent the most abundant molecular type in brain, with a fat content of ∼60% dry brain weight humans. Despite this fact, little attention has been paid to circumscribe dynamic role lipids function and disease. Membrane such as cholesterol, phosphoinositide, sphingolipids, arachidonic acid, endocannabinoids finely regulate both synaptic receptors ion channels that ensure critical neural functions. After brief introduction on their respective properties, we review here regulating channel activity, action potential propagation, neuronal development, functional plasticity contribution development neurological neuropsychiatric diseases. We also provide possible directions for future research lipid

Язык: Английский

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Role of lipid droplets in neurodegenerative diseases: From pathogenesis to therapeutics

Neuroscience & Biobehavioral Reviews, Год журнала: 2024, Номер 165, С. 105867 - 105867

Опубликована: Авг. 28, 2024

Neurodegenerative diseases (NDDs) are a series of disorders characterized by the progressive loss specific neurons, leading to cognitive and locomotor impairment. NDDs affect millions patients worldwide but lack effective treatments. Dysregulation lipids, particularly accumulation lipid droplets (LDs), is strongly implicated in pathogenesis NDDs. How LDs contribute occurrence development NDDs, their potential as therapeutic targets remain be addressed. In present review, we first introduce processes formation, transportation degradation. We then highlight how contributes cell type-specific manner. Moreover, discuss currently available methods for detecting elaborate on LDs-based strategies Lastly, identify gaps that need filled better leverage LD-based theranostics other diseases. hope this review could shed light role facilitate novel

Язык: Английский

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Arsenic Exposure Induces Neural Cells Senescence and Abnormal Lipid Droplet Accumulation Leading to Social Memory Impairment in Mice

Environmental Pollution, Год журнала: 2025, Номер 368, С. 125779 - 125779

Опубликована: Янв. 31, 2025

Язык: Английский

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Accumulation of Damaging Lipids in the Arf1‐Ablated Neurons Promotes Neurodegeneration through Releasing mtDNA and Activating Inflammatory Pathways in Microglia

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

Abstract Lipid metabolism disorders in both neurons and glial cells have been found neurodegenerative (ND) patients animal models. However, the pathological connection between lipid droplets NDs remains poorly understood. The recent work has highlighted utility of a neuron‐specific Arf1‐knockout mouse model corresponding for elucidating nexus amyotrophic lateral sclerosis (ALS) multiple (MS). In this study, it is that Arf1 deficiency first induced surplus fatty acid synthesis through AKT‐mTORC1‐SREBP1‐FASN axis, which further triggered endoplasmic reticulum (ER)‐mitochondrial stress cascade via calcium flux. organelle caused mitochondrial DNA (mtDNA) to be released into cytoplasm. Concurrently, FASN‐driven Arf1‐deficient might also induce accumulation sphingolipids lysosomes dysfunction autophagy lysosomes, promoted lysosomal mitochondria‐derived extracellular vesicles (MDEVs) release. MDEVs carried mtDNA microglia activate inflammatory pathways neurodegeneration. studies on neuronal (LDs) microglial LDs suggest unified function NDs: activating microglia. This finding potentially provides new therapeutic strategies NDs.

Язык: Английский

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Omega-3 EPA Supplementation Shapes the Gut Microbiota Composition and Reduces Major Histocompatibility Complex Class II in Aged Wild-Type and APP/PS1 Alzheimer’s Mice: A Pilot Experimental Study

Nutrients, Год журнала: 2025, Номер 17(7), С. 1108 - 1108

Опубликована: Март 21, 2025

Background/Objectives: Neuroinflammation, a hallmark of Alzheimer's disease (AD), is characterized by elevated levels inflammatory signaling molecules, including cytokines and eicosanoids, as well increased microglial reactivity, augmented gut microbiota dysbiosis via the gut-brain axis. We conducted pilot experiment to elucidate anti-inflammatory effects dietary omega-3 polyunsaturated fatty acid (ω-3 PUFA) eicosapentaenoic (EPA) on neuroinflammation. Methods: Female APP/PS1 mice (TG) non-transgenic littermates (WT), 13-14 months old, were fed diet supplemented with 0.3% EPA or control chow for 3 weeks. The composition, hippocampal plasma eicosanoids levels, platelet activation, phagocytosis, brain retinal genes protein expression, analyzed. Results: supplementation decreased percentage Bacteroidetes bacteria phylum Firmicutes in WT mice. Inflammatory lipid mediators hippocampus TG mice, accompanied reduction endocannabinoid docosahexaenoyl ethanolamide (DHEA). Dietary did not affect mediators, but reduced arachidonic-derived 5-HETE N-arachidonoylethanolamine (AEA) plasma. Moreover, major histocompatibility complex class II (MHCII) gene expression retina both genotypes, MHCII+ cells Conclusions: This study showed that short-term shaped increasing butyrate-producing decreasing Gram-negative LPS-producing phylum, downregulated marker MHCII two distinct regions central nervous system (CNS). Further investigation needed determine whether EPA-mediated microbiome have beneficial long-term AD pathology cognition.

Язык: Английский

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Lipid droplets in central nervous system and functional profiles of brain cells containing lipid droplets in various diseases

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Янв. 13, 2025

Lipid droplets (LDs), serving as the convergence point of energy metabolism and multiple signaling pathways, have garnered increasing attention in recent years. Different cell types within central nervous system (CNS) can regulate to generate or degrade LDs response diverse pathological stimuli. This article provides a comprehensive review on composition CNS, their generation degradation processes, interaction mechanisms with mitochondria, distribution among different types, roles played by these cells-particularly microglia astrocytes-in various prevalent neurological disorders. Additionally, we also emphasize paradoxical role post-cerebral ischemia inflammation explore potential underlying mechanisms, aiming identify novel therapeutic targets for this disease.

Язык: Английский

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Precise diabetes visualization designed for lipid droplet-targeted polarity-sensitive fluorescent probe

Microchemical Journal, Год журнала: 2025, Номер unknown, С. 113018 - 113018

Опубликована: Фев. 1, 2025

Язык: Английский

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Alterations in protein quality control resulting in neurodegeneration and disease

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 123 - 175

Опубликована: Янв. 1, 2025

Язык: Английский

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