Microglia in Alzheimer’s disease: pathogenesis, mechanisms, and therapeutic potentials DOI Creative Commons
Jifei Miao,

Haixia Ma,

Yang Yang

et al.

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

Published: June 15, 2023

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by protein aggregation in the brain. Recent studies have revealed critical role of microglia AD pathogenesis. This review provides comprehensive summary current understanding microglial involvement AD, focusing on genetic determinants, phenotypic state, phagocytic capacity, neuroinflammatory response, and impact synaptic plasticity neuronal regulation. Furthermore, recent developments drug discovery targeting are reviewed, highlighting potential avenues for therapeutic intervention. emphasizes essential insights into treatments.

Language: Английский

Brain-Gut-Microbiota Axis in Alzheimer’s Disease DOI Open Access
Karol Kowalski, Agata Mulak

Journal of Neurogastroenterology and Motility, Journal Year: 2019, Volume and Issue: 25(1), P. 48 - 60

Published: Jan. 10, 2019

Disturbances along the brain-gut-microbiota axis may significantly contribute to pathogenesis of neurodegenerative disorders. Alzheimer's disease (AD) is most frequent cause dementia characterized by a progressive decline in cognitive function associated with formation amyloid beta (Aβ) plaques and neurofibrillary tangles. Alterations gut microbiota composition induce increased permeability barrier immune activation leading systemic inflammation, which turn impair blood-brain promote neuroinflammation, neural injury, ultimately neurodegeneration. Recently, Aβ has also been recognized as an antimicrobial peptide participating innate response. However, dysregulated state, reveal harmful properties. Importantly, bacterial amyloids through molecular mimicry elicit cross-seeding misfolding microglial priming. The seeding propagation occur at different levels axis. potential mechanisms spreading include neuron-to-neuron or distal neuron spreading, direct crossing via other cells astrocytes, fibroblasts, microglia, system cells. A growing body experimental clinical data confirms key role dysbiosis microbiota-host interactions convergence gut-derived inflammatory response together aging poor diet elderly AD. Modification food-based therapy probiotic supplementation create new preventive therapeutic options

Language: Английский

Citations

648

Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview DOI Open Access
Núria Piqué, Mercedes Berlanga, David Miñana‐Galbis

et al.

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(10), P. 2534 - 2534

Published: May 23, 2019

Nowadays, the oral use of probiotics is widespread. However, safety profile with live still a matter debate. Main risks include: Cases systemic infections due to translocation, particularly in vulnerable patients and pediatric populations; acquisition antibiotic resistance genes; or interference gut colonization neonates. To avoid these risks, there an increasing interest non-viable microorganisms microbial cell extracts be used as probiotics, mainly heat-killed (including tyndallized) probiotic bacteria (lactic acid bifidobacteria). Heat-treated cells, cell-free supernatants, purified key components are able confer beneficial effects, immunomodulatory protection against enteropathogens, maintenance intestinal barrier integrity. At clinical level, products containing tyndallized strains have had role gastrointestinal diseases, including bloating infantile coli—in combination mucosal protectors—and diarrhea. Heat-inactivated could also management dermatological respiratory allergic diseases. The reviewed data indicate that their fractions advantages versus (mainly profile), positioning them interesting strategies for common prevalent conditions wide variety patients´ characteristics.

Language: Английский

Citations

463

Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease DOI Creative Commons
Estella A. Newcombe, Judith Camats‐Perna,

Mallone L. Silva

et al.

Journal of Neuroinflammation, Journal Year: 2018, Volume and Issue: 15(1)

Published: Sept. 24, 2018

Alzheimer’s disease (AD) is a neurodegenerative disorder, most cases of which lack clear causative event. This has made the difficult to characterize and, thus, diagnose. Although some are genetically linked, there many diseases and lifestyle factors that can lead an increased risk developing AD, including traumatic brain injury, diabetes, hypertension, obesity, other metabolic syndromes, in addition aging. Identifying common trends between these conditions could enhance our understanding AD development more effective treatments. immune system one body’s key defense mechanisms, chronic inflammation been increasingly linked with several age-related diseases. Moreover, it now well accepted important role onset progression AD. In this review, different inflammatory signals associated its will be outlined demonstrate how may influencing individual susceptibility Our goal bring attention potential shared presented by during successful

Language: Английский

Citations

457

Lipopolysaccharide-Induced Neuroinflammation as a Bridge to Understand Neurodegeneration DOI Open Access
Carla R.A. Batista, Giovanni Freitas Gomes, Eduardo Candelario‐Jalil

et al.

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(9), P. 2293 - 2293

Published: May 9, 2019

A large body of experimental evidence suggests that neuroinflammation is a key pathological event triggering and perpetuating the neurodegenerative process associated with many neurological diseases. Therefore, different stimuli, such as lipopolysaccharide (LPS), are used to model neurodegeneration. By acting at its receptors, LPS activates various intracellular molecules, which alter expression plethora inflammatory mediators. These factors, in turn, initiate or contribute development processes. an important tool for study However, serotype, route administration, number injections this toxin induce varied responses. Thus, here, we review use models neurodegeneration well discuss neuroinflammatory mechanisms induced by could underpin events linked process.

Language: Английский

Citations

416

The endotoxin hypothesis of neurodegeneration DOI Creative Commons
Guy C. Brown

Journal of Neuroinflammation, Journal Year: 2019, Volume and Issue: 16(1)

Published: Sept. 13, 2019

The endotoxin hypothesis of neurodegeneration is the that causes or contributes to neurodegeneration. Endotoxin a lipopolysaccharide (LPS), constituting much outer membrane gram-negative bacteria, present at high concentrations in gut, gums and skin other tissue during bacterial infection. Blood plasma levels are normally low, but elevated infections, gut inflammation, gum disease neurodegenerative disease. Adding such blood healthy humans induces systemic inflammation brain microglial activation. body rodents activation, priming and/or tolerance, memory deficits loss synapses neurons. promotes amyloid β tau aggregation neuropathology, suggesting possibility synergises with different aggregable proteins give diseases. Alzheimer's disease, which accelerated by including binds directly APOE, APOE4 variant both sensitises predisposes Intestinal permeability increases early Parkinson's injection into mice α-synuclein production aggregation, as well dopaminergic neurons substantia nigra. microbiome changes changing endotoxin-producing species can affect patients mouse models. amyotrophic lateral sclerosis, TDP-43 neuropathology. Peripheral diseases elevate endotoxin, sepsis, AIDS liver failure, also result indirectly activates microglia damage via nitric oxide, oxidants cytokines, phagocytosis unproven, if correct, then may be reduced decreasing endotoxin-induced neuroinflammation.

Language: Английский

Citations

374

Activation of microglia and astrocytes: a roadway to neuroinflammation and Alzheimer’s disease DOI
Darshpreet Kaur, Vivek Sharma, Rahul Deshmukh

et al.

Inflammopharmacology, Journal Year: 2019, Volume and Issue: 27(4), P. 663 - 677

Published: March 14, 2019

Language: Английский

Citations

372

Antibiotics, gut microbiota, and Alzheimer’s disease DOI Creative Commons
Francesco Angelucci,

Kateřina Čechová,

Jana Amlerová

et al.

Journal of Neuroinflammation, Journal Year: 2019, Volume and Issue: 16(1)

Published: May 22, 2019

Alzheimer's disease (AD) is a neurodegenerative whose various pathophysiological aspects are still being investigated. Recently, it has been hypothesized that AD may be associated with dysbiosis of microbes in the intestine. In fact, intestinal flora able to influence activity brain and cause its dysfunctions.Given growing interest this topic, purpose review analyze role antibiotics relation gut microbiota AD. first part review, we briefly theories supporting hypothesis can pathophysiology. second part, possible these events. Antibiotics normally used remove or prevent bacterial colonization human body, without targeting specific types bacteria. As result, broad-spectrum greatly affect composition microbiota, reduce biodiversity, delay for long period after administration. Thus, action could wide even opposite, depending on type antibiotic microbiome pathogenesis.Alteration induce changes activity, which raise possibility therapeutic manipulation other neurological disorders. This field research currently undergoing great development, but applications far away. Whether achieved using not known. The future depends progresses We must understand how when bacteria act promote Once well established, one think modifications use pre-, pro-, produce effects.

Language: Английский

Citations

372

Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease DOI
Periyanaina Kesika, Natarajan Suganthy, Bhagavathi Sundaram Sivamaruthi

et al.

Life Sciences, Journal Year: 2020, Volume and Issue: 264, P. 118627 - 118627

Published: Oct. 22, 2020

Language: Английский

Citations

359

Gut Microbiota and Dysbiosis in Alzheimer’s Disease: Implications for Pathogenesis and Treatment DOI Creative Commons
Shan Liu,

Jiguo Gao,

Mingqin Zhu

et al.

Molecular Neurobiology, Journal Year: 2020, Volume and Issue: 57(12), P. 5026 - 5043

Published: Aug. 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.

Language: Английский

Citations

335

Fecal Microbiota Transplantation in Neurological Disorders DOI Creative Commons
Karuna E.W. Vendrik, Rogier E. Ooijevaar,

Pieter R. C. de Jong

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2020, Volume and Issue: 10

Published: March 24, 2020

Background Several studies suggested an important role of the gut microbiota in pathophysiology neurological disorders, implying that alteration might serve as a treatment strategy. Fecal transplantation (FMT) is currently most effective intervention and accepted for recurrent Clostridioioides difficile infections. To evaluate indications FMT patients with we summarized available literature on FMT. In addition, provide suggestions future directions. Methods July 2019, five main databases were searched case descriptions disorders humans or animal models. ClinicalTrials.gov website was consulted registered planned ongoing trials. Results Of 541 identified studies, 34 included analysis. Clinical trials have been performed autism spectrum disorder showed beneficial effects symptoms. For multiple sclerosis Parkinson's disease, several positive effect FMT, supported by some reports humans. epilepsy, Tourette syndrome, diabetic neuropathy but evidence restricted to limited numbers studies. stroke, Alzheimer's disease Guillain-Barré syndrome only models identified. These potential healthy donor contrast, one study model stroke increased mortality after Whether findings from can be confirmed human diseases awaits seen. above mentioned are ongoing, well amyotrophic lateral sclerosis. Conclusions Preliminary suggests may promising option disorders. However, still scanty contrasting results observed. Limited while experiments conducted. Large double-blinded randomized controlled needed further elucidate

Language: Английский

Citations

328