Neuroinflammation in Alzheimer’s Disease

Biomedicines, Год журнала: 2021, Номер 9(5), С. 524 - 524

Опубликована: Май 7, 2021

Alzheimer's disease (AD) is a neurodegenerative associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise increasing age. There are currently no effective modifying treatments for AD, resulting in increasingly large socioeconomic personal costs. Increasing age an increase low-grade chronic inflammation (inflammaging) that may contribute the process AD. Although exact mechanisms remain unclear, aberrant elevation reactive oxygen nitrogen species (RONS) levels from several endogenous exogenous processes brain not only affect cell signaling, but also trigger cellular senescence, inflammation, pyroptosis. Moreover, compromised immune privilege allows infiltration peripheral cells infectious agents play role. Additionally, meta-inflammation as well gut microbiota dysbiosis drive neuroinflammatory process. Considering inflammatory/immune pathways dysregulated parallel cognitive dysfunction elucidating relationship between central nervous system facilitate development safe therapy We discuss some current ideas on inflammaging appear summarize details few immunomodulatory strategies being developed selectively target detrimental aspects neuroinflammation without affecting defense against pathogens tissue damage.

Язык: Английский

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The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options

Brain, Год журнала: 2021, Номер 144(9), С. 2571 - 2593

Опубликована: Апрель 12, 2021

Parkinson's disease is a common neurodegenerative disorder in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with shows unique changes, be used as early biomarkers disease. Alterations the composition related cause or effect non-motor symptoms, but specific pathogenic mechanisms are unclear. and its metabolites have been suggested involved pathogenesis by regulating neuroinflammation, barrier function neurotransmitter activity. There bidirectional communication between enteric nervous system CNS, microbiota-gut-brain axis provide pathway for transmission α-synuclein. We highlight recent discoveries about alterations focus on current mechanistic insights into pathophysiology. Moreover, we discuss interactions production α-synuclein inflammation neuroinflammation. In addition, draw attention diet modification, use probiotics prebiotics faecal transplantation potential therapeutic approaches that lead new treatment paradigm

Язык: Английский

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The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment

Nutrients, Год журнала: 2022, Номер 14(3), С. 668 - 668

Опубликована: Фев. 5, 2022

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation implicated in the pathogenesis several gastrointestinal extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through increasingly defined brain axis, opening possibility for new microbiota-based therapeutic options. Although studies conducted unravel possible relationship between Alzheimer’s Disease (AD) progression, diagnostic potential approaches aiming at restoring eubiosis remain be fully addressed. In this narrative review, we briefly summarize role homeostasis health disease, present evidence AD patients. Based on these observations, then discuss how dysbiosis might exploited tool early advanced stages, examine prebiotics, probiotics, fecal transplantation, diets complementary interventions thus offering insights into diagnosis treatment devastating progressive disease.

Язык: Английский

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Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Nutrients, Год журнала: 2021, Номер 13(2), С. 690 - 690

Опубликована: Фев. 21, 2021

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest GM can influence health host, several factors modify composition, such as diet, drug intake, lifestyle, geographical locations. Gut dysbiosis affect brain immune homeostasis through microbiota-gut-brain axis play key role pathogenesis neurodegenerative diseases, including dementia Alzheimer's disease (AD). relationship between AD is still elusive, but emerging evidence suggests it enhance secretion lipopolysaccharides amyloids may disturb intestinal permeability blood-brain barrier. In addition, promote hallmarks AD, oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, ultimately causation neural death. Poor dietary habits aging, along with inflammatory responses due to dysbiosis, contribute AD. Thus, modulation probiotics, or fecal transplantation could represent potential therapeutics this review, we discuss therapeutic strategies modulate

Язык: Английский

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Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Июнь 17, 2022

A consequence of our progressively ageing global population is the increasing prevalence worldwide age-related cognitive decline and dementia. In absence effective therapeutic interventions, identifying risk factors associated with becomes increasingly vital. Novel perspectives suggest that a dynamic bidirectional communication system between gut, its microbiome, central nervous system, commonly referred to as microbiota-gut-brain axis, may be contributing factor for health disease. However, exact mechanisms remain undefined. Microbial-derived metabolites produced in gut can cross intestinal epithelial barrier, enter systemic circulation trigger physiological responses both directly indirectly affecting functions. Dysregulation this (i.e., dysbiosis) modulate cytotoxic metabolite production, promote neuroinflammation negatively impact cognition. review, we explore critical connections microbial-derived (secondary bile acids, trimethylamine-N-oxide (TMAO), tryptophan derivatives others) their influence upon function neurodegenerative disorders, particular interest less-explored role decline.

Язык: Английский

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Immunological mechanisms of inflammatory diseases caused by gut microbiota dysbiosis: A review

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 164, С. 114985 - 114985

Опубликована: Июнь 11, 2023

The gut microbiota is indispensable for maintaining host health by enhancing the host's digestive capacity, safeguarding intestinal epithelial barrier, and preventing pathogen invasion. Additionally, exhibits a bidirectional interaction with immune system promotes of to mature. Dysbiosis microbiota, primarily caused factors such as genetic susceptibility, age, BMI, diet, drug abuse, significant contributor inflammatory diseases. However, mechanisms underlying diseases resulting from dysbiosis lack systematic categorization. In this study, we summarize normal physiological functions symbiotic in healthy state demonstrate that when occurs due various external factors, are lost, leading pathological damage lining, metabolic disorders, barrier damage. This, turn, triggers disorders eventually causes systems. These discoveries provide fresh perspectives on how diagnose treat unrecognized variables might affect link between illnesses need further studies extensive basic clinical research will still be required investigate relationship future.

Язык: Английский

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

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 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.

Язык: Английский

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Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis

Brain, Год журнала: 2023, Номер 146(12), С. 4916 - 4934

Опубликована: Окт. 18, 2023

Alzheimer's disease is a complex neurodegenerative disorder leading to decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor by showing specific alterations microbiome composition of patients rodent models. However, it unknown whether are causal manifestation symptoms. To understand involvement patient host physiology behaviour, we transplanted faecal from age-matched healthy controls into microbiota-depleted young adult rats. We found impairments behaviours reliant on hippocampal neurogenesis, essential process for certain memory functions mood, resulting transplants. Notably, severity correlated with clinical scores donor patients. Discrete changes rat caecal metabolome were also evident. As neurogenesis cannot be measured living humans but modulated circulatory systemic environment, assessed impact environment proxy readouts. Serum decreased human cells vitro associated key microbial genera. Our findings reveal first time, that symptoms can transferred organism via microbiota, confirming role disease, highlight converging central cellular regulating gut-mediated factors Alzheimer's.

Язык: Английский

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Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Июнь 19, 2023

Cognitive function in humans depends on the complex and interplay between multiple body systems, including hypothalamic-pituitary-adrenal (HPA) axis. The gut microbiota, which vastly outnumbers human cells has a genetic potential that exceeds of genome, plays crucial role this interplay. microbiota-gut-brain (MGB) axis is bidirectional signalling pathway operates through neural, endocrine, immune, metabolic pathways. One major neuroendocrine systems responding to stress HPA produces glucocorticoids such as cortisol corticosterone rodents. Appropriate concentrations are essential for normal neurodevelopment function, well cognitive processes learning memory, studies have shown microbes modulate throughout life. Stress can significantly impact MGB via other Animal research advanced our understanding these mechanisms pathways, leading paradigm shift conceptual thinking about influence microbiota health disease. Preclinical trials currently underway determine how animal models translate humans. In review article, we summarize current knowledge relationship axis, cognition, provide an overview main findings conclusions broad field.

Язык: Английский

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Vagus Nerve and Underlying Impact on the Gut Microbiota-Brain Axis in Behavior and Neurodegenerative Diseases

Journal of Inflammation Research, Год журнала: 2022, Номер Volume 15, С. 6213 - 6230

Опубликована: Ноя. 1, 2022

Abstract: The gut microbiota is the most abundant and diverse in human body vagus nerve widely distributed complex body, both of them are essential maintaining homeostasis. important phenomenon how they coordinate to regulate functions, which has attracted great attention scientists. academic literature on correlation with a host intestinal diseases even systemic revealed bidirectional communication between brain, can be carried out via multiple patterns. In review, firstly, we have general overview microbiota-brain axis. Secondly, according distribution characteristics nerve, analyzed summarized its function tract. At same time, underlying mechanism some behavior changes such as depressive anxiety-like behaviors related neurodegenerative caused by microecological environment disorders, then also inconsistency experimental evidence order propose novel strategies for clinical practice. Keywords: axis, microbiota, behavior,

Язык: Английский

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