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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Emerging diagnostics and therapeutics for Alzheimer disease

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(9), P. 2187 - 2199

Published: Sept. 1, 2023

Language: Английский

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Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies

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

Published: Aug. 23, 2024

Abstract Alzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate diverse, stemming from a combination factors such aging, genetics, environment. Our current understanding AD pathologies involves various hypotheses, cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, abnormal autophagy. Nonetheless, unraveling interplay among these pathological aspects pinpointing primary initiators require further elucidation validation. In past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available primarily offer symptomatic relief often accompanied by undesirable side However, recent approvals aducanumab ( 1 ) lecanemab 2 Food Drug Administration (FDA) present potential in disrease-modifying Nevertheless, long-term efficacy safety need Consequently, quest for safer more effective persists formidable pressing task. This review discusses pathogenesis, advances diagnostic biomarkers, latest updates trials, emerging technologies drug development. We highlight progress discovery selective inhibitors, dual-target allosteric modulators, covalent proteolysis-targeting chimeras (PROTACs), protein-protein interaction (PPI) modulators. goal provide insights into prospective development application novel drugs.

Language: Английский

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Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9577 - 9577

Published: May 31, 2023

The human gut microbiome contains the largest number of bacteria in body and has potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, diverse overall health. When becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, ageing, this profound effect on our health linked many diseases, including metabolic inflammatory neurological diseases. While humans largely association dysbiosis with disease, animal models, causative can be demonstrated. brain particularly important maintaining health, strong neurodegenerative neurodevelopmental This suggests that microbiota composition used make early diagnosis diseases modifying microbiome-gut-brain axis might present therapeutic target for have proved intractable, aim altering trajectory such as Alzheimer's Parkinson's multiple sclerosis, autism spectrum disorder, attention-deficit hyperactivity among others. other potentially reversible migraine, post-operative cognitive dysfunction, long COVID, which considered models therapy disease. role traditional methods microbiome, well newer, more novel treatments faecal transplants photobiomodulation, are discussed.

Language: Английский

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Role of Gut Microbiota in Neurological Disorders and Its Therapeutic Significance

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(4), P. 1650 - 1650

Published: Feb. 19, 2023

In humans, the gut microbiota (GM) are known to play a significant role in metabolism of nutrients and drugs, immunomodulation, pathogen defense by inhabiting gastrointestinal tract (GIT). The GM gut–brain axis (GBA) has been documented for different regulatory mechanisms associated pathways it shows behaviors with individualized bacteria. addition, as susceptibility factor neurological disorders central nervous system (CNS), regulating disease progression being amenable intervention. Bidirectional transmission between brain occurs GBA, implying that performs neurocrine, endocrine, immune-mediated signaling pathways. regulates multiple supplementing them prebiotics, probiotics, postbiotics, synbiotics, fecal transplantations, and/or antibiotics. A well-balanced diet is critically important establishing healthy GM, which can alter enteric (ENS) regulate disorders. Here, we have discussed function GBA from gut, neurology interacts various GM. Furthermore, highlighted recent advances future prospects may require addressing research concerns about

Language: Английский

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Gut microbiome-targeted therapies for Alzheimer’s disease

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(2)

Published: Nov. 7, 2023

The advent of high­throughput ‘omics’ technologies has improved our knowledge gut microbiome in human health and disease, including Alzheimer’s disease (AD), a neurodegenerative disorder. Frequent bidirectional communications mutual regulation exist between the gastrointestinal tract central nervous system through gut-brain axis. A large body research reported close association microbiota AD development, restoring healthy may curb or even improve symptoms progression. Thus, modulation become novel paradigm for clinical management AD, emerging effort focused on developing potential strategies preventing and/or treating disease. In this review, we provide an overview connection causal relationship dysbiosis mechanisms driving progression, successes challenges implementing available microbiome-targeted therapies (including probiotics, prebiotics, synbiotics, postbiotics, fecal transplantation) preventive therapeutic preclinical intervention studies AD. Finally, discuss future directions field.

Language: Английский

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Efficacy of Probiotic Supplements on Brain-Derived Neurotrophic Factor, Inflammatory Biomarkers, Oxidative Stress and Cognitive Function in Patients with Alzheimer’s Dementia: A 12-Week Randomized, Double-Blind Active-Controlled Study

Nutrients, Journal Year: 2023, Volume and Issue: 16(1), P. 16 - 16

Published: Dec. 20, 2023

The role of neurotrophic factors, oxidative stress, and inflammation in the pathogenesis Alzheimer's disease (AD) has been explored. Animal studies have reported positive effects probiotics on these factors. Some clinical also support potential improving cognitive function via gut-brain axis older adults. However, experimental evaluating efficacy targeting factors inflammatory biomarkers, particularly among AD patients, remain very limited. In this randomized, double-blinded, active-controlled trial, we used multi-strain probiotic supplements, including

Language: Английский

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Neuropathogenesis-on-chips for neurodegenerative diseases

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 12, 2024

Abstract Developing diagnostics and treatments for neurodegenerative diseases (NDs) is challenging due to multifactorial pathogenesis that progresses gradually. Advanced in vitro systems recapitulate patient-like pathophysiology are emerging as alternatives conventional animal-based models. In this review, we explore the interconnected pathogenic features of different types ND, discuss general strategy modelling NDs using a microfluidic chip, introduce organoid-on-a-chip next advanced relevant model. Lastly, overview how these models being applied academic industrial drug development. The integration chips, stem cells, biotechnological devices promises provide valuable insights biomedical research developing diagnostic therapeutic solutions NDs.

Language: Английский

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Curcumin Mitigates the High-Fat High-Sugar Diet-Induced Impairment of Spatial Memory, Hepatic Metabolism, and the Alteration of the Gut Microbiome in Alzheimer’s Disease-Induced (3xTg-AD) Mice

Nutrients, Journal Year: 2024, Volume and Issue: 16(2), P. 240 - 240

Published: Jan. 12, 2024

The escalating prevalence of metabolic diseases and an aging demographic has been correlated with a concerning rise in Alzheimer's disease (AD) incidence. This study aimed to access the protective effects curcumin, bioactive flavonoid from turmeric, on spatial memory, functions, regulation gut microbiome AD-induced (3xTg-AD) mice fed either normal chow diet (NCD) or high-fat high-sugar (HFHSD). Our findings revealed augmented susceptibility HFHSD-fed 3xTg-AD for weight gain memory impairment, while curcumin supplementation demonstrated effect against these changes. was evidenced by significantly reduced body improved behavioral cognitive function curcumin-treated group. These improvements were substantiated diminished fatty acid synthesis, altered cholesterol metabolism, suppressed adipogenesis-related pathways liver, along modified synaptic plasticity-related brain. Moreover, enriched beneficial microbiota, including

Language: Английский

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Alzheimer’s disease and drug delivery across the blood–brain barrier: approaches and challenges

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: June 8, 2024

Abstract Alzheimer's disease (AD) is a diverse with complex pathophysiology. The presence of extracellular β-amyloid deposition as neuritic plaques and intracellular accumulation hyper-phosphorylated tau neurofibrillary tangles remain the core neuropathologic criteria for diagnosing disease. Nonetheless, several recent basic discoveries have revealed significant pathogenic roles other essential cellular molecular processes. Previously, there were not so many disease-modifying medications (DMT) available drug distribution through blood–brain barrier (BBB) difficult due to its nature, especially drugs polypeptides nature proteins. Recently FDA has approved lecanemab DMT proven efficacy. It also complicated deliver diseases like epilepsy or any brain tumor limitations BBB. After advancements in delivery system, different techniques are used transport medication across Other methods used, enhancement blood vessel fluidity by liposomes, infusion hyperosmotic solutions, local intracerebral implants, but these invasive approaches. Non-invasive approaches include formulation nanoparticles their coating polymers. This review article emphasizes all above-mentioned techniques, procedures, challenges transporting medicines summarizes most literature dealing

Language: Английский

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