Roles of tau protein in health and disease

Acta Neuropathologica, Год журнала: 2017, Номер 133(5), С. 665 - 704

Опубликована: Апрель 6, 2017

Tau is well established as a microtubule-associated protein in neurons. However, under pathological conditions, aberrant assembly of tau into insoluble aggregates accompanied by synaptic dysfunction and neural cell death range neurodegenerative disorders, collectively referred to tauopathies. Recent advances our understanding the multiple functions different locations inside outside neurons have revealed novel insights its importance diverse molecular pathways including signalling, plasticity, regulation genomic stability. The present review describes physiological pathophysiological properties how these relate distribution We highlight post-translational modifications tau, which are pivotal defining modulating localisation roles health disease. include discussion other pathologically relevant changes mutation aggregation, aspects impinge on propensity propagate, potentially drive neuronal loss, diseased brain. Finally, we describe cascade events that may be driven dysfunction, impaired axonal transport, alterations synapse mitochondrial function, activation unfolded response defective degradation. It important fully understand attributed since this will provide vital information involvement development pathogenesis Such knowledge enable determination critical should targeted potential therapeutic agents developed for treatment

Язык: Английский

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Gut Microbiota is Altered in Patients with Alzheimer’s Disease

Journal of Alzheimer s Disease, Год журнала: 2018, Номер 63(4), С. 1337 - 1346

Опубликована: Май 11, 2018

Previous studies suggest that gut microbiota is associated with neuropsychiatric disorders, such as Parkinson's disease, amyotrophic lateral sclerosis, and depression. However, whether the composition diversity of altered in patients Alzheimer's disease (AD) remains large ly unknown. In present study, we collected fecal samples from 43 AD age- gender-matched cognitively normal controls. 16S ribosomal RNA sequencing technique was used to analyze feces. The different between two groups. Several bacteria taxa were those controls at taxonomic levels, Bacteroides, Actinobacteria, Ruminococcus, Lachnospiraceae, Selenomonadales. Our findings may be involved pathogenesis AD.

Язык: Английский

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Gut microbiota: A player in aging and a target for anti-aging intervention

Ageing Research Reviews, Год журнала: 2017, Номер 35, С. 36 - 45

Опубликована: Янв. 18, 2017

Язык: Английский

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Antibiotics, gut microbiota, and Alzheimer’s disease

Journal of Neuroinflammation, Год журнала: 2019, Номер 16(1)

Опубликована: Май 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.

Язык: Английский

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(Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease

Microbiome, Год журнала: 2017, Номер 5(1)

Опубликована: Июль 14, 2017

Chronic inflammation represents one of the most consistent biologic features aging. However, precise etiology persistent low-grade increases in remains unclear. Recent evidence suggests that gut microbiome may play a key role age-related inflammation. Indeed, several studies have indicated older adults display an altered composition microbiota, and early indicates this dysbiosis is associated with presence circulating inflammatory analytes. The present review summarizes knowledge on discusses how potential relationships lead to novel treatment strategies future. “The pattern disease expression response man his total environment (physical, biological, social); is, therefore, determined by anything affects himself or environment.” – Rene Dubos, 1961

Язык: Английский

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Structural changes of gut microbiota in Parkinson’s disease and its correlation with clinical features

Science China Life Sciences, Год журнала: 2017, Номер 60(11), С. 1223 - 1233

Опубликована: Май 20, 2017

Язык: Английский

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Alteration of the fecal microbiota in Chinese patients with Parkinson’s disease

Brain Behavior and Immunity, Год журнала: 2018, Номер 70, С. 194 - 202

Опубликована: Март 2, 2018

Язык: Английский

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Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer's Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus

Frontiers in Cellular and Infection Microbiology, Год журнала: 2017, Номер 7

Опубликована: Июль 11, 2017

Although the potential contribution of human gastrointestinal (GI) tract microbiome to health, aging and disease is becoming increasingly acknowledged, molecular mechanics signaling pathways just how this accomplished not well understood. Major bacterial species GI tract, such as abundant Gram-negative bacilli Bacteroides fragilis (B. fragilis) Escherichia coli (E. coli), secrete a remarkably complex array pro-inflammatory neurotoxins which, when released from confines healthy are pathogenic highly detrimental homeostatic function neurons in central nervous system (CNS). For first time here we report presence lipopolysaccharide (LPS) brain lysates hippocampus superior temporal lobe neocortex Alzheimer's (AD) brains. Mean LPS levels varied 2-fold increases 3-fold hippocampus, AD over age-matched controls, however some samples advanced hippocampal cases exhibited up 26-fold increase controls. This 'Perspectives' paper will further highlight very recent research on CNS, update current findings that implicate microbiome-derived an important internal contributor inflammatory degeneration CNS.

Язык: Английский

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Fecal Microbiota Transplantation in Neurological Disorders

Frontiers in Cellular and Infection Microbiology, Год журнала: 2020, Номер 10

Опубликована: Март 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

Язык: Английский

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Probiotics modulate the microbiota–gut–brain axis and improve memory deficits in aged SAMP8 mice

Acta Pharmaceutica Sinica B, Год журнала: 2019, Номер 10(3), С. 475 - 487

Опубликована: Июль 7, 2019

ProBiotic-4 is a probiotic preparation composed of Bifidobacterium lactis, Lactobacillus casei, bifidum, and acidophilus. This study aims to investigate the effects on microbiota-gut-brain axis cognitive deficits, explore underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. was orally administered 9-month-old SAMP8 mice for 12 weeks. We observed that significantly improved memory cerebral neuronal synaptic injuries, glial activation, microbiota composition in feces brains aged substantially attenuated aging-related disruption intestinal barrier blood-brain barrier, decreased interleukin-6 tumor necrosis factor-α at both mRNA protein levels, reduced plasma lipopolysaccharide (LPS) concentration, toll-like receptor 4 (TLR4) expression, nuclear factor-κB (NF-κB) translocation brain. In addition, not only did levels γ-H2AX, 8-hydroxydesoxyguanosine, retinoic-acid-inducible gene-I (RIG-I), it also abrogated RIG-I multimerization These findings suggest targeting gut with probiotics may have therapeutic potential deficits function aging, its associated inhibition TLR4-and RIG-I-mediated NF-κB signaling pathway inflammatory responses.

Язык: Английский

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