Alzheimer Disease: An Update on Pathobiology and Treatment Strategies

Cell, Journal Year: 2019, Volume and Issue: 179(2), P. 312 - 339

Published: Sept. 26, 2019

Language: Английский

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Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(7), P. 426 - 440

Published: Jan. 28, 2021

Language: Английский

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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease

Molecular Neurodegeneration, Journal Year: 2020, Volume and Issue: 15(1)

Published: July 16, 2020

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder seen in age-dependent dementia. There currently no effective treatment for AD, which may be attributed part to lack of a clear underlying mechanism. Studies within last few decades provide growing evidence central role amyloid β (Aβ) and tau, as well glial contributions various molecular cellular pathways AD pathogenesis. Herein, we review recent progress with respect Aβ- tau-associated mechanisms, discuss dysfunction emphasis on neuronal receptors that mediate Aβ-induced toxicity. We also other critical factors affect pathogenesis, including genetics, aging, variables related environment, lifestyle habits, describe potential apolipoprotein E (APOE), viral bacterial infection, sleep, microbiota. Although have gained much towards understanding aspects this devastating disorder, greater commitment research mechanism, diagnostics will needed future research.

Language: Английский

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Role of neuroinflammation in neurodegeneration development

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 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.

Language: Английский

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

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 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.

Language: Английский

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Alzheimer's disease drug development pipeline: 2020

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2020, Volume and Issue: 6(1)

Published: Jan. 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

Language: 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, Journal Year: 2020, Volume and Issue: 64, P. 101174 - 101174

Published: Sept. 21, 2020

Language: Английский

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The oral microbiome: Role of key organisms and complex networks in oral health and disease

Periodontology 2000, Journal Year: 2021, Volume and Issue: 87(1), P. 107 - 131

Published: Aug. 31, 2021

Abstract States of oral health and disease reflect the compositional functional capacities of, as well interspecies interactions within, microbiota. The cavity exists a highly dynamic microbial environment that harbors many distinct substrata microenvironments house diverse communities. Specific to cavity, nonshedding dental surfaces facilitate development complex polymicrobial biofilm communities, characterized not only by microbes comprising them, but cumulatively their activities. Adding this complexity, faces near‐constant environmental challenges, including those from host diet, salivary flow, masticatory forces, introduction exogenous microbes. composition microbiome is shaped throughout life factors genetics, maternal transmission, factors, such dietary habits, hygiene practice, medications, systemic factors. This ecosystem presents opportunities for dysbiosis periodontal diseases. application both in vitro culture‐independent approaches has broadened mechanistic understandings communities within environmental, local, underpinnings influence dynamics microbiome. Here, we review present knowledge current understanding influences challenges upon system encourage homeostasis or provoke perturbation, thus contribute states disease.

Language: Английский

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The Human Oral Microbiome in Health and Disease: From Sequences to Ecosystems

Microorganisms, Journal Year: 2020, Volume and Issue: 8(2), P. 308 - 308

Published: Feb. 23, 2020

The human oral cavity is home to an abundant and diverse microbial community (i.e., the microbiome), whose composition roles in health disease have been focus of intense research recent years. Thanks developments sequencing-based approaches, such as 16S ribosomal RNA metabarcoding, whole metagenome shotgun sequencing, or meta-transcriptomics, we now can efficiently explore diversity microbes, even if unculturable. Recent studies charted ecosystems how they change due lifestyle conditions. As progress, there increasing evidence important role microbiome conditions, which are not limited diseases cavity. This, turn, opens new avenues for microbiome-based diagnostics therapeutics that benefit from easy accessibility monitoring manipulation. Yet, many challenges remain ahead. In this review, survey main methodologies currently used highlight major findings enabled by these approaches. Finally, discuss future prospects field.

Language: Английский

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Oral microbiota in human systematic diseases

International Journal of Oral Science, Journal Year: 2022, Volume and Issue: 14(1)

Published: March 2, 2022

Abstract Oral bacteria directly affect the disease status of dental caries and periodontal diseases. The dynamic oral microbiota cooperates with host to reflect information immunity metabolism through two-way communication along cavity systemic organs. is one most important interaction windows between human body environment. microenvironment at different sites in has microbial compositions regulated by complex signaling, hosts, external environmental factors. These processes may or health because certain states seem be related composition bacteria, destruction community In this review, we discussed emerging exciting evidence connections microbes multiple diseases, possible contribution microorganisms This review aims enhance interest on whole body, also improve clinician’s understanding role Microbial research dentistry potentially enhances our knowledge pathogenic mechanisms same time, continuous advances frontier field lead a tangible impact health.

Language: Английский

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