Metabolomics integrated with mass spectrometry imaging reveals novel action of tetramethylpyrazine in migraine

Food Chemistry, Год журнала: 2024, Номер 460, С. 140614 - 140614

Опубликована: Июль 26, 2024

Язык: Английский

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Transcriptome analysis of early‐ and late‐onset Alzheimer's disease in Korean cohorts

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(2)

Опубликована: Фев. 1, 2025

Abstract INTRODUCTION The molecular mechanisms underlying early‐onset Alzheimer's disease (EOAD) and late‐onset (LOAD) remain incompletely understood, particularly in Asian populations. METHODS RNA‐sequencing was carried out on blood samples from 248 participants the Seoul National University Bundang Hospital cohort to perform differential gene expression (DGE) weighted co‐expression network analysis. Findings were replicated an independent Korean ( N = 275). RESULTS DGE analysis identified 18 88 dysregulated genes EOAD LOAD, respectively. Network a LOAD‐associated module showing significant enrichment pathways related mitophagy, 5′ adenosine monophosphate‐activated protein kinase signaling, ubiquitin‐mediated proteolysis. In replication cohort, downregulation of SMOX PLVAP LOAD replicated, highly preserved. addition, associated with brain amyloid beta deposition. DISCUSSION Our findings suggest distinct signatures for population, providing deeper understanding their diagnostic potential mechanisms. Highlights Analysis (LOAD), Expression levels downregulated LOAD. Pathways including mitophagy signaling enriched module. A preserved across two cohorts.

Язык: Английский

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Cognitive vulnerability to glucose fluctuations: A digital phenotype of neurodegeneration

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(2)

Опубликована: Фев. 1, 2025

Cognition is reduced at low and high glucose, reflecting cognitive vulnerability to glucose (CVG) fluctuations. The impact of fluctuations on the aging brain remains unclear. We examined whether CVG associated with plasma biomarkers Alzheimer's disease (AD) pathology neurodegeneration. Participants included N = 114 adults type 1 diabetes assessed for processing speed sustained attention using ecological momentary assessment (EMA) combined continuous monitoring (CGM). characterized associations between amyloid beta (Aβ) 42/40, phosphorylated tau (p-tau) 181 217, neurofilament light chain, glial fibrillary acidic protein. was all biomarkers, except Aβ 42/40. exhibited strong p-tau that persisted across covariate specifications. may be a useful digital phenotype AD. It unclear contributes versus arises from consider possible mechanisms linking long-term variability development neuropathology. Cognitive used investigate CVG's biomarkers. Associations remained significant covariates. discuss relating variability, cognition,

Язык: Английский

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Huntington disease oligodendrocyte maturation deficits revealed by single-nucleus RNAseq are rescued by thiamine-biotin supplementation

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Дек. 21, 2022

Abstract The complexity of affected brain regions and cell types is a challenge for Huntington’s disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex striatum from R6/2 mice human HD post-mortem tissue. We identify type-specific -agnostic signatures suggesting oligodendrocytes (OLs) oligodendrocyte precursors (OPCs) are arrested intermediate maturation states. OL-lineage regulators OLIG1 OLIG2 negatively correlated with CAG length OPCs, ATACseq analysis mouse NeuN-negative cells shows decreased accessibility regulated by OL genes. data implicates glucose lipid metabolism abnormal PRKCE Thiamine Pyrophosphokinase 1 ( TPK1 ) as central Thiamine/biotin treatment R6/1 compensate dysregulation restores rescues neuronal pathology. Our insights into spans multiple link deficits thiamine metabolism.

Язык: Английский

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Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(17), С. 10073 - 10073

Опубликована: Сен. 3, 2022

The human brain is characterised by the most diverse morphological, metabolic and functional structure among all body tissues. This due to existence of neurons secreting various neurotransmitters mutually modulating their own activity through thousands pre- postsynaptic interconnections in each neuron. Astroglial, microglial oligodendroglial cells reciprocally regulate metabolism key energy substrates, thereby exerting several neuroprotective, neurotoxic regulatory effects on neuronal viability neurotransmitter functions. Maintenance pool mitochondrial acetyl-CoA derived from glycolytic glucose a factor for survival. Thus, regarded as direct precursor TCA cycle respiratory chain, affecting cell viability. It also used hundreds acetylation reactions, including N-acetyl aspartate synthesis mitochondria, acetylcholine cholinergic neurons, well divergent acetylations proteins, peptides, histones low-molecular-weight species cellular compartments. Therefore, should be considered central point maintaining equilibrium between anabolic catabolic pathways brain. review presents data supporting this thesis.

Язык: Английский

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Impact of glucose metabolism on the developing brain

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Дек. 23, 2022

Glucose is the most important substrate for proper brain functioning and development, with an increased glucose consumption in relation to need of creating new structures connections. Therefore, alterations homeostasis will inevitably be associated changes development Nervous System. Several studies demonstrated how alteration - both hyper hypoglycemia- may interfere cognitivity, including deficits intelligence quotient, anomalies learning memory, as well differences executive functions. Importantly, structure functionality were found after a single episode diabetic ketoacidosis suggesting importance glycemic control stressing screening programs type 1 diabetes protect children from this dramatic condition. The exciting progresses neuroimaging techniques such diffusion tensor imaging, has helped improve understanding effects, outcomes mechanisms underlying following dysglycemia, lead more insights on physio-pathological related neurological consequences about hypoglycemia.

Язык: Английский

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Osteocalcin ameliorates cognitive dysfunctions in a mouse model of Alzheimer’s Disease by reducing amyloid β burden and upregulating glycolysis in neuroglia

Cell Death Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Фев. 6, 2023

Alzheimer's disease (AD) is the most common neurodegenerative characterized by accumulation of amyloid β peptides (Aβ) and impaired glucose metabolism in brain. Osteocalcin (OCN), an osteoblast-derived protein, has been shown to modulate brain functions but whether it any effect on AD undetermined. In this study, daily intraperitoneal injection OCN for 4 weeks ameliorated anxiety-like behaviors cognitive dysfunctions APP/PS1 transgenic mice model, as increased entries into central area open field test, time arms elevated plus maze spent light chamber light-dark transition well reduced escape latency preference target quadrant Morris water test. Aβ burden hippocampus cortex was OCN. Besides, improved neural network function brain, mainly enhanced power high gamma band medial prefrontal mice. The proliferation astrocytes also inhibited demonstrated immunofluorescence. Furthermore, glycolysis microglia, evidenced consumption, lactate production, extracellular acidification rate. Such abolished when receptor - Gpr158 knockdown astrocytes. Our study revealed a novel therapeutic factor potentially through reducing upregulation neuroglia.

Язык: Английский

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Iron and Targeted Iron Therapy in Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(22), С. 16353 - 16353

Опубликована: Ноя. 15, 2023

Alzheimer’s disease (AD) is the most common neurodegenerative worldwide. β-amyloid plaque (Aβ) deposition and hyperphosphorylated tau, as well dysregulated energy metabolism in brain, are key factors progression of AD. Many studies have observed abnormal iron accumulation different regions AD which closely correlated with clinical symptoms AD; therefore, understanding role brain major pathological aspects critical for its treatment. This review discusses main mechanisms recent advances involvement above processes, including iron-induced oxidative stress-dependent non-dependent directions, summarizes hypothesis that dysregulation may be an initiating factor AD, based on available evidence, further therapeutic perspectives targeting iron.

Язык: Английский

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Advancements in Brain Research: The In Vivo/In Vitro Electrochemical Detection of Neurochemicals

Biosensors, Год журнала: 2024, Номер 14(3), С. 125 - 125

Опубликована: Фев. 26, 2024

Neurochemicals, crucial for nervous system function, influence vital bodily processes and their fluctuations are linked to neurodegenerative diseases mental health conditions. Monitoring these compounds is pivotal, yet the intricate nature of central poses challenges. Researchers have devised methods, notably electrochemical sensing with micro-nanoscale electrodes, offering high-resolution monitoring despite low concentrations rapid changes. Implantable sensors enable precise detection in brain tissues minimal damage, while microdialysis-coupled platforms allow vivo sampling subsequent vitro analysis, addressing selectivity issues seen other methods. While lacking temporal resolution, techniques like HPLC CE complement sensing’s selectivity, particularly structurally similar neurochemicals. This review covers essential neurochemicals explores miniaturized emphasizing microdialysis integration. It discusses pros cons techniques, forecasting future neuroscience research. Overall, this comprehensive outlines evolution, strengths, potential applications study neurochemicals, insights into advancements field.

Язык: Английский

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Metformin: A promising drug for human cancers (Review)

Oncology Letters, Год журнала: 2022, Номер 24(1)

Опубликована: Май 12, 2022

Small-molecule chemical drugs are of great significance for tumor-targeted and individualized therapies. However, the development new small-molecule drugs, from basic experimental research clinical trials to final application in practice, is a long process that has high cost. It takes at least 5 years most be developed laboratory prove their effectiveness safety. Compared with repurposing traditional non-tumor can shortcut. Metformin good model use an old drug. In recent years, antitumor efficacy metformin attracted much attention. Epidemiological data vivo, vitro experiments have shown reduce incidence cancer patients diabetes strong antagonistic effect on metabolism-related tumors. Recent studies induce autophagy esophageal cells, mainly by inhibiting inflammatory signaling pathways. functions mechanisms multifaceted. The present study aims review tumor prevention treatment.

Язык: Английский

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