Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression

Cell Research, Год журнала: 2019, Номер 29(10), С. 787 - 803

Опубликована: Сен. 6, 2019

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet role of microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link neuroinflammation progression. Using mouse models, discovered that, during alteration composition leads to peripheral accumulation phenylalanine isoleucine, which stimulates differentiation proliferation pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated Th1 immune cells are associated with M1 microglia activation, contributing AD-associated neuroinflammation. Importantly, elevation isoleucine concentrations increase cell frequency blood were also observed two small independent cohorts patients mild cognitive impairment (MCI) due AD. Furthermore, GV-971, sodium oligomannate that demonstrated solid consistent cognition improvement phase 3 clinical trial China, suppresses phenylalanine/isoleucine accumulation, harnesses reverses impairment. Together, our findings highlight dysbiosis-promoted progression suggest novel strategy for therapy by remodelling microbiota.

Язык: Английский

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Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Дек. 16, 2022

Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue cell functions significant increases the risks of various aging-related diseases, including neurodegenerative cardiovascular metabolic musculoskeletal immune system diseases. Although development modern medicine has promoted human health greatly extended life expectancy, aging society, variety chronic diseases have gradually become most important causes disability death elderly individuals. Current research on focuses elucidating how endogenous exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss proteostasis, compromise autophagy, mitochondrial cellular senescence, stem exhaustion, altered intercellular communication, deregulated nutrient sensing) participate regulation aging. Furthermore, thorough pathogenesis to identify interventions that promote longevity caloric restriction, microbiota transplantation, nutritional intervention) clinical treatment methods for (depletion senescent cells, therapy, antioxidative anti-inflammatory treatments, hormone replacement therapy) could decrease incidence turn healthy longevity.

Язык: Английский

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Diet and Inflammation in Cognitive Ageing and Alzheimer’s Disease

Current Nutrition Reports, Год журнала: 2019, Номер 8(2), С. 53 - 65

Опубликована: Апрель 4, 2019

Nutrition is known to modulate the immune system and may alter neuroinflammatory processes implicated in pathogenesis of Alzheimer's disease (AD) progression neurodegeneration. Here, we review evidence for healthy dietary patterns age-related cognition discuss potential actions diet on cognitive function. Anti-inflammatory such as Mediterranean (MD) approaches stop hypertension (DASH) be neuroprotective. Several components consumed MD DASH (omega-3 fatty acids, antioxidants polyphenols) can inhibit neuroinflammation associated with AD. diets also attenuate via indirect pathways from gut microbiome systemic circulation. Diet influence ageing several inflammatory pathways. However, data human studies are lacking exact mechanisms linking function remain elusive. Further intervention required investigate diet-associated neurological change earliest through latest stages decline. Furthermore, incorporation neuroimaging measures would advance current understanding mechanistic effects modification brain.

Язык: Английский

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Microglia, Lifestyle Stress, and Neurodegeneration

Immunity, Год журнала: 2020, Номер 52(2), С. 222 - 240

Опубликована: Янв. 7, 2020

Язык: Английский

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Western diet as a trigger of Alzheimer’s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration

Ageing Research Reviews, Год журнала: 2021, Номер 70, С. 101397 - 101397

Опубликована: Июнь 30, 2021

An excess of saturated fatty acids and simple sugars in the diet is a known environmental risk factor Alzheimer's disease (AD) but holistic view interacting processes through which such may contribute to AD pathogenesis missing. We addressed this need extensive analysis published studies investigating effects western (WD) on development humans laboratory animals. reviewed WD-induced systemic alterations comprising metabolic changes, induction obesity adipose tissue inflammation, gut microbiota dysbiosis acceleration low-grade inflammation. Next we provide an overview evidence demonstrating that WD-associated drive impairment blood-brain barrier (BBB) neuroinflammation paralleled by accumulation toxic amyloid. Later these changes are followed dysfunction synaptic transmission, neurodegeneration finally memory cognitive impairment. conclude WD can trigger inflammaging, BBB induced inflammation play central role process. Moreover, concurrence Aβ dyshomeostasis, reciprocal interactions vicious cycle neurodegeneration, contradicts as primary AD. Given 2019 World Health Organization recommended focusing modifiable factors prevention, sequential, complex pathomechanisms initiated WD, lead from peripheral disturbances support future prevention strategies.

Язык: Английский

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The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame?

Nutrients, Год журнала: 2020, Номер 13(1), С. 37 - 37

Опубликована: Дек. 24, 2020

For years, it has been reported that Alzheimer’s disease (AD) is the most common cause of dementia. Various external and internal factors may contribute to early onset AD. This review highlights a contribution disturbances in microbiota–gut–brain (MGB) axis development Alteration gut microbiota composition determined by increase permeability barrier immune cell activation, leading impairment blood–brain function promotes neuroinflammation, neuronal loss, neural injury, ultimately Numerous studies have shown plays crucial role brain changes behavior individuals formation bacterial amyloids. Lipopolysaccharides amyloids synthesized can trigger cells residing activate response neuroinflammation. Growing experimental clinical data indicate prominent dysbiosis microbiota–host interactions Modulation with antibiotics or probiotic supplementation create new preventive therapeutic options Accumulating evidences affirm research on MGB involvement AD necessary for treatment targets therapies

Язык: Английский

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Neuropathology of Alzheimer's Disease

Neurotherapeutics, Год журнала: 2021, Номер 19(1), С. 173 - 185

Опубликована: Ноя. 2, 2021

Язык: Английский

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Gut microbiota of aquatic organisms: A key endpoint for ecotoxicological studies

Environmental Pollution, Год журнала: 2019, Номер 248, С. 989 - 999

Опубликована: Март 2, 2019

Язык: Английский

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The complexity of Alzheimer’s disease: an evolving puzzle

Physiological Reviews, Год журнала: 2021, Номер 101(3), С. 1047 - 1081

Опубликована: Янв. 21, 2021

The history of Alzheimer's disease (AD) started in 1907, but we needed to wait until the end century identify components pathological hallmarks and genetic subtypes formulate first pathogenic hypothesis. Thanks biomarkers new technologies, concept AD then rapidly changed from a static view an amnestic dementia presenium biological entity that could be clinically manifested as normal cognition or different types. What is clearly emerging studies heterogeneous each aspect, such amyloid composition, tau distribution, relation between tau, clinical symptoms, background, thus it probably impossible explain with single process. scientific approach suffers chronological mismatches clinical, pathological, technological data, causing difficulty conceiving diagnostic gold standards creating models for drug discovery screening. A recent mathematical computer-based offers opportunity study real life provide point final missing pieces puzzle.

Язык: Английский

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Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease

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

Опубликована: Март 5, 2022

The implication of gut microbiota in the control brain functions health and disease is a novel, currently emerging concept. Accumulating data suggest that exert its action at least part by modulating neuroinflammation. Given link between neuroinflammatory changes neuronal activity, it plausible may affect indirectly impacting microglia, key player Indeed, increasing evidence suggests interplay microglia synaptic dysfunction involve microbiota, among other factors. In addition to these indirect microglia-dependent actions on has been recently recognized could also activity directly stimulation vagus nerve.

Язык: Английский

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