Integrative metabolomics science in Alzheimer’s disease: Relevance and future perspectives

Ageing Research Reviews, Год журнала: 2023, Номер 89, С. 101987 - 101987

Опубликована: Июнь 19, 2023

Язык: Английский

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Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer’s disease

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 18, 2024

Abstract Dietary protein is a critical regulator of metabolic health and aging. Low diets are associated with healthy aging in humans, dietary restriction extends the lifespan healthspan mice. In this study, we examined effect (PR) on development progression Alzheimer’s disease (AD) 3xTg mouse model AD. Here, show that PR promotes leanness glycemic control mice, specifically rescuing glucose intolerance females. induces sex-specific alterations circulating brain metabolites, downregulating sphingolipid subclasses also reduces AD pathology mTORC1 activity, increases autophagy, improves cognition Finally, survival Our results suggest or pharmaceutical interventions mimic effects diet may hold promise as treatment for

Язык: Английский

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Brain high-throughput multi-omics data reveal molecular heterogeneity in Alzheimer’s disease

PLoS Biology, Год журнала: 2024, Номер 22(4), С. e3002607 - e3002607

Опубликована: Апрель 30, 2024

Unbiased data-driven omic approaches are revealing the molecular heterogeneity of Alzheimer disease. Here, we used machine learning to integrate high-throughput transcriptomic, proteomic, metabolomic, and lipidomic profiles with clinical neuropathological data from multiple human AD cohorts. We discovered 4 unique multimodal profiles, one them showing signs poor cognitive function, a faster pace disease progression, shorter survival disease, severe neurodegeneration astrogliosis, reduced levels metabolomic profiles. found this profile be present in affected cortical regions associated higher Braak tau scores significant dysregulation synapse-related genes, endocytosis, phagosome, mTOR signaling pathways altered early late stages. cross-omics integration transcriptomic an SNCA mouse model revealed overlapping signature. Furthermore, leveraged single-nuclei RNA-seq identify distinct cell-types that most likely mediate Lastly, identified clusters uncovered cerebrospinal fluid biomarkers poised monitor progression possibly cognition. Our analyses provide novel critical insights into AD.

Язык: Английский

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Advance computational tools for multiomics data learning

Biotechnology Advances, Год журнала: 2024, Номер 77, С. 108447 - 108447

Опубликована: Сен. 7, 2024

Язык: Английский

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Dapagliflozin Ameliorates Cognitive Impairment in Aluminum-Chloride-Induced Alzheimer’s Disease via Modulation of AMPK/mTOR, Oxidative Stress and Glucose Metabolism

Pharmaceuticals, Год журнала: 2023, Номер 16(5), С. 753 - 753

Опубликована: Май 16, 2023

Alzheimer's disease (AD) is a progressive neurological illness characterized by memory loss and cognitive deterioration. Dapagliflozin was suggested to attenuate the impairment associated with AD; however, its mechanisms were not fully elucidated. This study aims examine possible of neuroprotective effects dapagliflozin against aluminum chloride (AlCl3)-induced AD. Rats distributed into four groups: group 1 received saline, 2 AlCl3 (70 mg/kg) daily for 9 weeks, groups 3 4 administered 5 weeks. (1 (5 then given another Two behavioral experiments performed: Morris Water Maze (MWM) Y-maze spontaneous alternation (Y-maze) task. Histopathological alterations in brain, as well changes acetylcholinesterase (AChE) amyloid β (Aβ) peptide activities oxidative stress (OS) markers, all evaluated. A western blot analysis used detection phosphorylated 5' AMP-activated protein kinase (p-AMPK), mammalian target Rapamycin (p-mTOR) heme oxygenase-1 (HO-1). Tissue samples collected isolation glucose transporters (GLUTs) glycolytic enzymes using PCR analysis, brain levels also measured. The current data demonstrate that represents approach combat AlCl3-induced AD rats through inhibiting stress, enhancing metabolism activating AMPK signaling.

Язык: Английский

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Advancing personalized medicine: Integrating statistical algorithms with omics and nano-omics for enhanced diagnostic accuracy and treatment efficacy

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер 1870(7), С. 167339 - 167339

Опубликована: Окт. 1, 2024

Язык: Английский

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Molecular Biomarkers in Neurological Diseases: Advances in Diagnosis and Prognosis

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 2231 - 2231

Опубликована: Март 1, 2025

Neurological diseases contribute significantly to disability and mortality, necessitating improved diagnostic prognostic tools. Advances in molecular biomarkers at genomic, transcriptomic, epigenomic, proteomic levels have facilitated early disease detection. Notably, neurofilament light chain (NfL) serves as a key biomarker of neurodegeneration, while liquid biopsy techniques enable non-invasive monitoring through exosomal tau, α-synuclein, inflammatory markers. Artificial intelligence (AI) multi-omics integration further enhance discovery, promoting precision medicine. A comprehensive literature review was conducted using PubMed, Scopus, Web Science identify studies (2010-2024) on neurodegenerative neuroinflammatory disorders. Key findings genomic mutations, transcriptomic signatures, epigenetic modifications, protein-based were analyzed. The highlight the potential approaches improving accuracy therapeutic stratification. Genomic, markers demonstrate utility detection monitoring. AI-driven analysis enhances discovery clinical application. Despite advancements, challenges remain validation, standardization, implementation. Large-scale longitudinal are essential ensure reliability. AI-powered may accelerate application, ultimately patient outcomes neurological diseases.

Язык: Английский

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Cerebrospinal Fluid Metabolomics and Proteomics Integration in Neurological Syndromes

Methods in molecular biology, Год журнала: 2025, Номер unknown, С. 303 - 321

Опубликована: Янв. 1, 2025

Язык: Английский

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Advancing Alzheimer's Therapy: Computational Strategies and Treatment Innovations

IBRO Neuroscience Reports, Год журнала: 2025, Номер 18, С. 270 - 282

Опубликована: Фев. 4, 2025

Alzheimer's disease (AD) is a multifaceted neurodegenerative condition distinguished by the occurrence of memory impairment, cognitive deterioration, and neuronal impairment. Despite extensive research efforts, conventional treatment strategies primarily focus on symptom management, highlighting need for innovative therapeutic approaches. This review explores challenges AD integration computational methodologies to advance interventions. A comprehensive analysis recent literature was conducted elucidate broad scope etiology limitations drug discovery Our findings underscore critical role models in elucidating mechanisms, identifying targets, expediting discovery. Through simulations, researchers can predict efficacy, optimize lead compounds, facilitate personalized medicine Moreover, machine learning algorithms enhance early diagnosis enable precision analyzing multi-modal datasets. Case studies highlight application techniques therapeutics, including suppression crucial proteins implicated progression repurposing existing drugs management. Computational interplay between oxidative stress neurodegeneration, offering insights into potential Collaborative efforts biologists, pharmacologists, clinicians are essential translate clinically actionable interventions, ultimately improving patient outcomes addressing unmet medical needs individuals affected AD. Overall, integrating represents promising paradigm shift solutions overcome transform landscape treatment.

Язык: Английский

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xOmicsShiny: an R shiny application for cross-omics data analysis and pathway mapping

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

Abstract Summary We developed xOmicsShiny, a feature-rich R Shiny-powered application that enables biologists to fully explore omics datasets across experiments and data types, with an emphasis on uncovering biological insights at the pathway level. The merging feature ensures flexible exploration of cross-omics data, such as transcriptomics, proteomics, metabolomics, lipidomics. mapping function covers broad range databases, including WikiPathways, Reactome, KEGG pathways. In addition, xOmicsShiny offers several visualization options analytical tasks for everyday analysis, namely, PCA, Volcano plot, Venn Diagram, Heatmap, WGCNA, advanced clustering analyses. employs customizable modules perform various tasks, generating both interactive plots publication-ready figures. This dynamic, modular design overcomes issue slow loading in Shiny tools allows it be readily expanded by research developer community. Availability implementation is publicly available at: http://xOmicsShiny.bxgenomics.com . Researchers can upload their own server or use pre-loaded demo dataset. source code, under MIT license provided https://github.com/interactivereport/xOmicsShiny local installation. A full tutorial https://interactivereport.github.io/xOmicsShiny/tutorial/docs/index.html Contact [email protected] [email protected] Supplementary are bioRxiv online.

Язык: Английский

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