Alzheimer's disease

The Lancet, Год журнала: 2021, Номер 397(10284), С. 1577 - 1590

Опубликована: Март 2, 2021

Язык: Английский

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The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication

Frontiers in Endocrinology, Год журнала: 2020, Номер 11

Опубликована: Янв. 31, 2020

A substantial body of evidence supports that the gut microbiota plays a pivotal role in regulation metabolic, endocrine and immune functions. In recent years, there has been growing recognition involvement modulation multiple neurochemical pathways through highly interconnected gut-brain axis. Although amazing scientific breakthroughs over last few years have expanded our knowledge on communication between microbes their hosts, underpinnings microbiota-gut-brain crosstalk remain to be determined. Short-chain fatty acids (SCFAs), main metabolites produced colon by bacterial fermentation dietary fibers resistant starch, are speculated play key neuro-immunoendocrine regulation. However, underlying mechanisms which SCFAs might influence brain physiology behavior not fully elucidated. this review, we will outline current about interactions. We also highlight how development future treatments for central nervous system (CNS) disorders can take advantage intimate mutual interactions with exploring function.

Язык: Английский

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The gut microbiota–brain axis in behaviour and brain disorders

Nature Reviews Microbiology, Год журнала: 2020, Номер 19(4), С. 241 - 255

Опубликована: Окт. 22, 2020

Язык: Английский

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Clinical trials of new drugs for Alzheimer disease

Journal of Biomedical Science, Год журнала: 2020, Номер 27(1)

Опубликована: Янв. 6, 2020

Abstract Alzheimer disease (AD) accounts for 60–70% of dementia cases. Given the seriousness and continual increase in patient numbers, developing effective therapies to treat AD has become urgent. Presently, drugs available treatment, including cholinesterase inhibitors an antagonist N-methyl-D-aspartate receptor, can only inhibit symptoms a limited period time but cannot stop or reverse progression. On basis amyloid hypothesis, many global drug companies have conducted clinical trials on clearing therapy without success. Thus, hypothesis may not be completely feasible. The number anti-amyloid decreased 2019, which might turning point. An in-depth comprehensive understanding contribution beta other factors is crucial novel pharmacotherapies. In ongoing trials, researchers developed are testing several possible interventions aimed at various targets, anti-tau interventions, neurotransmitter modification, anti-neuroinflammation neuroprotection cognitive enhancement, relieve behavioral psychological symptoms. this article, we present current state clinicaltrials.gov . We reviewed underlying mechanisms these tried understand reason why prior failed, analyzed future trend trials.

Язык: Английский

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The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Дек. 10, 2020

The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is condition associated not only with gastrointestinal disorders but diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect central nervous system (CNS) inflammation. tract are communicating through bidirectional network of signaling pathways called gut-brain axis, which consists multiple connections, including vagus nerve, immune system, bacterial metabolites products. During these dysregulated altered permeability blood-brain barrier (BBB) neuroinflammation. However, numerous mechanisms behind impact gut neuro-development -pathogenesis remain poorly understood. There several involved CNS homeostasis Among those, inflammasome pathway been linked to neuroinflammatory conditions such sclerosis, Alzheimer’s Parkinson’s diseases, anxiety depressive-like disorders. complex assembles upon cell activation due exposure microbes, danger signals, or stress lead production pro-inflammatory cytokines (interleukin-1β interleukin-18) pyroptosis. Evidences suggest there reciprocal influence brain. how this precisely working yet be discovered. Herein, we discuss status knowledge open questions field focusing on function products cells during healthy inflammatory conditions, neuropsychiatric In particular, focus innate mechanism certain microbes.

Язык: Английский

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Role of neuroinflammation in neurodegeneration development

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июль 12, 2023

Abstract Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s so on, have suggested that inflammation is not only a result of neurodegeneration but also crucial player this process. Protein aggregates which are very common pathological phenomenon can induce neuroinflammation further aggravates protein aggregation neurodegeneration. Actually, even happens earlier than aggregation. Neuroinflammation induced by genetic variations CNS cells or peripheral immune may deposition some susceptible population. Numerous signaling pathways range been to be involved the pathogenesis neurodegeneration, although they still far from being completely understood. Due limited success traditional treatment methods, blocking enhancing inflammatory considered promising strategies for therapy many them got exciting results animal models clinical trials. Some them, few, approved FDA usage. Here we comprehensively review factors affecting major pathogenicity sclerosis. We summarize current strategies, both clinic, diseases.

Язык: Английский

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Alzheimer's disease drug development pipeline: 2020

Alzheimer s & Dementia Translational Research & Clinical Interventions, Год журнала: 2020, Номер 6(1)

Опубликована: Янв. 1, 2020

Abstract Introduction Alzheimer's disease (AD) is a growing public health concern affecting millions of patients worldwide and costing billions dollars annually. We review the pipeline drugs biologics in clinical trials for treatment AD. use Common Related Dementias Research Ontology (CADRO) to classify targets mechanisms action. our annual reports past 5 years provide longitudinal insight into drug development Methods reviewed ClinicalTrials.gov as February 27, 2020, identified all pharmacologic agents currently being developed AD represented on this widely used U.S. Food Drug Administration registry. Results There are 121 Twenty‐nine 36 Phase 3 trials, 65 73 2 27 1 trials. Twelve target cognitive enhancement 12 intended treat neuropsychiatric behavioral symptoms. 97 modification Compared 2019 pipeline, there an increase number disease‐modifying targeting pathways other than amyloid or tau. Discussion The 2020 has innovations that hope greater success programs. Review over show progressive emphasis non‐amyloid targets, including candidate treatments inflammation, synapse neuronal protection, vascular factors, neurogenesis, epigenetic interventions. been marked growth repurposed pipeline. image

Язык: Английский

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A research agenda for ageing in China in the 21st century (2nd edition): Focusing on basic and translational research, long-term care, policy and social networks

Ageing Research Reviews, Год журнала: 2020, Номер 64, С. 101174 - 101174

Опубликована: Сен. 21, 2020

Язык: Английский

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Role and Mechanism of Gut Microbiota in Human Disease

Frontiers in Cellular and Infection Microbiology, Год журнала: 2021, Номер 11

Опубликована: Март 17, 2021

The human gut microbiome is a huge microbial community that plays an irreplaceable role in life. With the further development of research, influence intestinal flora on diseases has been gradually excavated. Gut microbiota (GM) dysbiosis adverse health effects body will lead to variety chronic diseases. underlying mechanisms GM are incredibly complicated. This review focuses regulation and mechanism neurodegenerative diseases, cardiovascular metabolic gastrointestinal thus providing potential target for prevention treatment disease.

Язык: Английский

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Gut Microbiota and Dysbiosis in Alzheimer’s Disease: Implications for Pathogenesis and Treatment

Molecular Neurobiology, Год журнала: 2020, Номер 57(12), С. 5026 - 5043

Опубликована: Авг. 22, 2020

Understanding how gut flora influences gut-brain communications has been the subject of significant research over past decade. The broadening term "microbiota-gut-brain axis" from "gut-brain underscores a bidirectional communication system between and brain. microbiota-gut-brain axis involves metabolic, endocrine, neural, immune pathways which are crucial for maintenance brain homeostasis. Alterations in composition microbiota associated with multiple neuropsychiatric disorders. Although causal relationship dysbiosis neural dysfunction remains elusive, emerging evidence indicates that may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, insulin resistance pathogenesis Alzheimer's disease (AD). Illustration mechanisms underlying regulation by pave way developing novel therapeutic strategies AD. In this narrative review, we provide an overview their dysregulation Novel insights into modification as preventive or approach AD highlighted.

Язык: Английский

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