New progress in the pharmacology of protocatechuic acid: A compound ingested in daily foods and herbs frequently and heavily

Pharmacological Research, Journal Year: 2020, Volume and Issue: 161, P. 105109 - 105109

Published: July 30, 2020

Language: Английский

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Causal Relationship between Diet-Induced Gut Microbiota Changes and Diabetes: A Novel Strategy to Transplant Faecalibacterium prausnitzii in Preventing Diabetes

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(12), P. 3720 - 3720

Published: Nov. 22, 2018

The incidence of metabolic disorders, including diabetes, has elevated exponentially during the last decades and enhanced risk a variety complications, such as diabetes cardiovascular diseases. In present review, we have highlighted new insights on complex relationships between diet-induced modulation gut microbiota diabetes. Literature from various library databases electronic searches (ScienceDirect, PubMed, Google Scholar) were randomly collected. There exists relationship diet microbiota, which alters energy balance, health impacts, autoimmunity, further causes inflammation dysfunction, Faecalibacterium prausnitzii is butyrate-producing bacterium, plays vital role in Transplantation F. been used an intervention strategy to treat dysbiosis gut’s microbial community that linked inflammation, precedes autoimmune disease review focuses literature highlights benefits especially, abundant protecting pattern its therapeutic potential against

Language: Английский

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Emerging role of gut microbiota in modulation of neuroinflammation and neurodegeneration with emphasis on Alzheimer's disease

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2020, Volume and Issue: 106, P. 110112 - 110112

Published: Sept. 16, 2020

Language: Английский

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New approaches to symptomatic treatments for Alzheimer’s disease

Molecular Neurodegeneration, Journal Year: 2021, Volume and Issue: 16(1)

Published: Jan. 13, 2021

Successful development of agents that improve cognition and behavior in Alzheimer's disease (AD) is critical to improving the lives patients manifesting symptoms this progressive disorder.There have been no recent approvals cognitive enhancing for AD. There are currently 6 enhancers Phase 2 trials 4 phase 3. They represent a variety novel mechanisms. has progress developing new treatments neuropsychiatric AD with advances treatment insomnia, psychosis, apathy, agitation AD-related psychotropic 7 3 trials. Many mechanisms being explored behavioral targets. Progress trial designs, outcomes measures, population definitions conduct symptomatic AD.Advances combined enhanced methods promise address unmet needs improved amelioration symptoms.

Language: Английский

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Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(700)

Published: June 14, 2023

Alzheimer’s disease (AD) pathology is thought to progress from normal cognition through preclinical and ultimately symptomatic AD with cognitive impairment. Recent work suggests that the gut microbiome of patients has an altered taxonomic composition compared healthy, cognitively control individuals. However, knowledge about changes in before onset limited. In this cross-sectional study accounted for clinical covariates dietary intake, we microbial function a cohort 164 individuals, 49 whom showed biomarker evidence early AD. Gut profiles individuals were distinct those without The change correlated β-amyloid (Aβ) tau pathological biomarkers but not neurodegeneration, suggesting may process. We identified specific bacterial taxa associated Inclusion these features improved accuracy, sensitivity, specificity machine learning classifiers predicting status when tested on subset (65 participants). correlates neuropathology improve our understanding etiology help identify gut-derived markers risk.

Language: Английский

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The extracellular vesicle of gut microbial Paenalcaligenes hominis is a risk factor for vagus nerve-mediated cognitive impairment

Microbiome, Journal Year: 2020, Volume and Issue: 8(1)

Published: July 15, 2020

Abstract Background In a pilot study, we found that feces transplantation from elderly individuals to mice significantly caused cognitive impairment. Paenalcaligenes hominis and Escherichia coli are increasingly detected in the of adults aged mice. Therefore, isolated examined their effects on occurrence age-related degenerative impairment colonic inflammation Results The collected people more severe transplanted young than those Oral gavage strong colitis specific pathogen-free (SPF) germ-free also induced SPF , its extracellular vesicles (EVs), and/or lipopolysaccharide However, celiac vagotomy inhibited impairment, but not colitis, exposed or EVs, whereas had no such effects. Vagotomy infiltration EVs into hippocampus. Conclusions particularly can cause function-impaired disorders, as Alzheimer’s disease, may penetrate brain through blood well vagus nerve.

Language: Английский

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APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: Sept. 24, 2022

Abstract ApoE is the major lipid and cholesterol carrier in CNS. There are three human polymorphisms, apoE2, apoE3, apoE4, genetic expression of APOE4 one most influential risk factors for development late-onset Alzheimer's disease (AD). Neuroinflammation has become third hallmark AD, together with Amyloid-β plaques neurofibrillary tangles hyperphosphorylated aggregated tau protein. This review aims to broadly extensively describe differential aspects concerning apoE. Starting from evolution apoE how APOE's single-nucleotide polymorphisms affect its structure, function, involvement during health disease. reflects on impact critical AD pathology, such as neuroinflammatory response, particularly effect APOE astrocytic microglial function dynamics, synaptic amyloid-β load, autophagy, cell–cell communication. We discuss affecting pathology combined genotype, sex, age, diet, physical exercise, current therapies clinical trials field. The genotype other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, multiple also addressed. Therefore, this gathers relevant findings related up date implications CNS pathologies provide a deeper understanding knowledge

Language: Английский

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

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 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.

Language: Английский

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Novel Therapeutic Approaches for Alzheimer’s Disease: An Updated Review

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(15), P. 8208 - 8208

Published: July 30, 2021

Alzheimer's disease (AD) is a progressive neurodegenerative and accounts for most cases of dementia. The prevalence AD has increased in the current rapidly aging society contributes to heavy burden on families society. Despite profound impact AD, treatments are unable achieve satisfactory therapeutic effects or stop progression disease. Finding novel become urgent. In this paper, we reviewed approaches five categories: anti-amyloid therapy, anti-tau anti-neuroinflammatory neuroprotective agents including N-methyl-D-aspartate (NMDA) receptor modulators, brain stimulation. trend development shifting from single pathological target more complex mechanism, such as neuroinflammatory processes. While drug repositioning may accelerate pharmacological development, non-pharmacological interventions, especially repetitive transcranial magnetic stimulation (rTMS) direct (tDCS), also have potential clinical application. future, it possible physicians choose appropriate interventions individually basis precision medicine.

Language: Английский

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

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: June 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.

Language: Английский

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