Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

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Apolipoprotein E in lipid metabolism and neurodegenerative disease

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 34(8), P. 430 - 445

Published: June 24, 2023

Dysregulation of lipid metabolism has emerged as a central component many neurodegenerative diseases. Variants the transport protein, apolipoprotein E (APOE), modulate risk and resilience in several diseases including late-onset Alzheimer's disease (LOAD). Allelic variants gene, APOE, alter cells tissues have been broadly associated with other cellular systemic phenotypes. Targeting APOE-associated metabolic pathways may offer opportunities to disease-related phenotypes consequently, attenuate impart multiple We review molecular, cellular, tissue-level alterations that arise from different APOE isoforms. These changes could help elucidate mechanisms tune resilience.

Language: Английский

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Cell type-specific roles of APOE4 in Alzheimer disease

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(2), P. 91 - 110

Published: Jan. 8, 2024

Language: Английский

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Integrative multi-omics and systems bioinformatics in translational neuroscience: A data mining perspective

Journal of Pharmaceutical Analysis, Journal Year: 2023, Volume and Issue: 13(8), P. 836 - 850

Published: July 1, 2023

Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth information, with its application to neuroscience termed neuroinformatics. Data mining enabled the generation new hypotheses based on differentially regulated biological molecules associated disease mechanisms, which can be tested experimentally for improved diagnostic therapeutic targeting neurodegenerative diseases. Importantly, integrating multi-omics data using systems bioinformatics approach will advance understanding layered interactive network regulation that exchanges systemic knowledge facilitate development comprehensive human brain profile. In this review, we first summarize studies utilizing from individual type analysis, including epigenetics/epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, spatial omics, pertaining Alzheimer's disease, Parkinson's multiple sclerosis. We then discuss integration approaches, independent unsupervised methods, more intuitive informative interpretation obtained across different layers. further assess integrate provide convoluted insights offer proof-of-concept proposition towards reconstruction networks. Finally, recommend combination high dimensional experimental validation achieve translational applications biomarker discovery, development, elucidation mechanisms. conclude future perspectives opportunities applying integrative precision phenotyping diseases personalized medicine.

Language: Английский

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APOE ε4 associates with microglial activation independently of Aβ plaques and tau tangles

Science Advances, Journal Year: 2023, Volume and Issue: 9(14)

Published: April 5, 2023

Animal studies suggest that the apolipoprotein E ε4 (

Language: Английский

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Multifaceted roles of APOE in Alzheimer disease

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(8), P. 457 - 474

Published: June 21, 2024

Language: Английский

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Neuroinflammation and immunometabolism in neurodegenerative diseases

Current Opinion in Neurology, Journal Year: 2025, Volume and Issue: 38(2), P. 163 - 171

Published: Feb. 12, 2025

Immunometabolism is an emerging field of research investigating the ability immune cells to modulate their metabolic activity for optimal function. While this has been extensively examined in peripheral like macrophages, only recently have these studies extended assess immunometabolic microglia, innate brain. Microglia are highly metabolically flexible and can utilize different nutrients diverse functions. Like other cells, they undergo reprogramming on stimulation inflammatory, neurodegenerative conditions such as Alzheimer's disease (AD). In recent years, researchers looked at intricate mechanisms that microglial uncovered key links between altered metabolism, neuroinflammation, involvement disease-associated risk genes. This review highlights significantly contributed our understanding dysregulation observed activated microglia AD, unveiling novel targets therapeutic intervention.

Language: Английский

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Roles of ApoE4 on the Pathogenesis in Alzheimer’s Disease and the Potential Therapeutic Approaches

Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 43(7), P. 3115 - 3136

Published: May 25, 2023

Language: Английский

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Cellular senescence in brain aging and cognitive decline

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Nov. 23, 2023

Cellular senescence is a biological aging hallmark that plays key role in the development of neurodegenerative diseases. Clinical trials are currently underway to evaluate effectiveness senotherapies for these However, impact on brain and cognitive decline absence neurodegeneration remains uncertain. Moreover, patient populations like cancer survivors, traumatic injury obese individuals, obstructive sleep apnea patients, chronic kidney disease patients can suffer age-related changes prematurely, suggesting they may accelerated brain. Understanding neurocognitive deficits linked conditions crucial, especially considering rapidly evolving field senotherapeutics. Such treatments could help alleviate early significantly reducing morbidity healthcare costs. This review provides translational perspective how cellular decline. We also discuss important caveats surrounding mainstream senolytics senomorphics, present emerging evidence hyperbaric oxygen therapy immune-directed therapies as viable modalities senescent cell burden.

Language: Английский

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Current views on meningeal lymphatics and immunity in aging and Alzheimer’s disease

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: Aug. 14, 2023

Abstract Alzheimer’s disease (AD) is an aging-related form of dementia associated with the accumulation pathological aggregates amyloid beta and neurofibrillary tangles in brain. These phenomena are accompanied by exacerbated inflammation marked neuronal loss, which altogether contribute to accelerated cognitive decline. The multifactorial nature AD, allied our still limited knowledge its etiology pathophysiology, have lessened capacity develop effective treatments for AD patients. Over last few decades, genome wide association studies biomarker development, alongside mechanistic experiments involving animal models, identified different immune components that play key roles modulation brain pathology affecting progression severity. As we will relay this review, much recent efforts been directed better understanding role innate immunity, particularly microglia. However, despite lack diversity within resident cells, border tissues, especially meninges, harbour a considerable number types subtypes adaptive cells. Alongside microglia, taken centre stage as important players research, there new exciting evidence pointing namely T B cells found modulators neuroinflammation (dys)function AD. Importantly, genuine functional lymphatic vascular network present around outermost meningeal layer, dura. lymphatics directly connected peripheral system mammalian species, including humans, crucial preserving “healthy” surveillance CNS, shaping responses, not only locally at but also level tissue. In provide comprehensive view on current about vasculature, emphasizing described modulating CNS fluid macromolecule drainage, well glial function aging

Language: Английский

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