Mechanisms and pathology of protein misfolding and aggregation

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(12), P. 912 - 933

Published: Sept. 8, 2023

Language: Английский

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Gut Microbiome–Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(10), P. 1717 - 1763

Published: May 8, 2023

Gut microbiota includes a vast collection of microorganisms residing within the gastrointestinal tract. It is broadly recognized that gut and brain are in constant bidirectional communication, which its metabolic production major component, form so-called microbiome–brain axis. Disturbances homeostasis caused by imbalance their functional composition activities, known as dysbiosis, cause dysregulation these pathways trigger changes blood–brain barrier permeability, thereby causing pathological malfunctions, including neurological disorders. In turn, can affect structure function through autonomic nervous system regulating motility, intestinal transit secretion, permeability. Here, we examine data from CAS Content Collection, largest published scientific information, analyze publication landscape recent research. We review advances knowledge related to human microbiome, complexity functionality, communication with central system, effect axis on mental health. discuss correlations between various diseases, specifically also explore metabolites regard impact associated diseases. Finally, assess clinical applications gut-microbiota-related substances development pipelines. hope this serve useful resource understanding current emerging field an effort further solving remaining challenges fulfilling potential.

Language: Английский

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Emerging role of the host microbiome in neuropsychiatric disorders: overview and future directions

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(9), P. 3625 - 3637

Published: Sept. 1, 2023

Abstract The human body harbors a diverse ecosystem of microorganisms, including bacteria, viruses, and fungi, collectively known as the microbiota. Current research is increasingly focusing on potential association between microbiota various neuropsychiatric disorders. resides in parts body, such oral cavity, nasal passages, lungs, gut, skin, bladder, vagina. gut gastrointestinal tract has received particular attention due to its high abundance role psychiatric neurodegenerative However, presents other tissues, though less abundant, also plays crucial immune system homeostasis, thus influencing development progression For example, imbalance associated periodontitis might increase risk for Additionally, studies using postmortem brain samples have detected widespread presence bacteria brains patients with Alzheimer’s disease. This article provides an overview emerging host disorders discusses future directions, underlying biological mechanisms, reliable biomarkers microbiota, microbiota-targeted interventions, this field.

Language: Английский

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Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer’s disease: a randomized, controlled clinical trial

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: June 7, 2024

Abstract Background Evidence links lifestyle factors with Alzheimer’s disease (AD). We report the first randomized, controlled clinical trial to determine if intensive changes may beneficially affect progression of mild cognitive impairment (MCI) or early dementia due AD. Methods A 1:1 multicenter randomized phase 2 trial, ages 45-90 MCI AD and a Montreal Cognitive Assessment (MoCA) score 18 higher. The primary outcome measures were in cognition function tests: Clinical Global Impression Change (CGIC), Disease Scale (ADAS-Cog), Dementia Rating–Sum Boxes (CDR-SB), Rating (CDR-G) after 20 weeks an multidomain intervention compared wait-list usual care control group. ADAS-Cog, CDR-SB, CDR-Global scales using Mann-Whitney-Wilcoxon rank-sum test, CGIC was Fisher’s exact test. Secondary outcomes included plasma Aβ42/40 ratio, other biomarkers, correlating degree change these measures. Results Fifty-one patients enrolled, mean age 73.5. No significant differences any at baseline. Only two withdrew. All had ratios <0.0672 baseline, strongly supporting diagnosis. After weeks, between-group ( p = 0.001), CDR-SB 0.032), CDR 0.037) tests borderline significance ADAS-Cog test 0.053). CGIC, Global, showed improvement significantly less progression, group which worsened all four ratio increased decreased 0.003). There correlation between both ratio. microbiome improved only <0.0001). Conclusions Comprehensive improve many Trial registration Approved by Western Institutional Review Board on 12/31/2017 (#20172897) Boards sites. This study registered retrospectively clinicaltrials.gov October 8, 2020 (NCT04606420, ID: 20172897).

Language: Английский

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Exploring the Influence of Gut–Brain Axis Modulation on Cognitive Health: A Comprehensive Review of Prebiotics, Probiotics, and Symbiotics

Nutrients, Journal Year: 2024, Volume and Issue: 16(6), P. 789 - 789

Published: March 10, 2024

Recent research exploring the relationship between gut and brain suggests that condition of microbiota can influence cognitive health. A well-balanced may help reduce inflammation, which is linked to neurodegenerative conditions. Prebiotics, probiotics, symbiotics are nutritional supplements functional food components associated with gastrointestinal well-being. The bidirectional communication gut–brain axis essential for maintaining homeostasis, pre-, pro-, potentially affecting various functions such as attention, perception, memory. Numerous studies have consistently shown incorporating into a healthy diet lead improvements in mood. Maintaining support optimal function, crucial disease prevention our fast-paced, Westernized society. Our results indicate benefits older individuals probiotic supplementation but not who good adequate levels physical activity. Additionally, it appears there patients mild impairment Alzheimer’s disease, while mixed seem arise younger healthier individuals. However, important acknowledge individual responses vary, use these dietary should be tailored each individual’s unique health circumstances needs.

Language: Английский

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Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Feb. 27, 2024

The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS) Huntington's (HD), are complex multifaceted. A growing body evidence suggests that the gut microbiome plays crucial roles in development progression diseases. Clinicians have come to realize therapeutics targeting potential halt This narrative review examines alterations AD, PD, ALS HD, highlighting close relationship between brain Processes mediate microbiome-brain communication including immunological, vagus nerve circulatory pathways, evaluated. Furthermore, we summarize for diseases modify its metabolites, diets, probiotics prebiotics, microbial antibacterials faecal transplantation. Finally, current challenges future directions discussed.

Language: Английский

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Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer’s disease mouse models

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 8, 2024

Abstract The gut microbiota and microglia play critical roles in Alzheimer’s disease (AD), elevated Bacteroides is correlated with cerebrospinal fluid amyloid-β (Aβ) tau levels AD. We hypothesize that contributes to AD by modulating microglia. Here we show administering fragilis APP/PS1-21 mice increases Aβ plaques females, modulates cortical amyloid processing gene expression, down regulates phagocytosis protein degradation microglial expression. further aged wild-type male female suppresses uptake of Aβ1-42 injected into the hippocampus. Depleting murine Bacteroidota metronidazole decreases load 5xFAD mice, activates pathways related phagocytosis, cytokine signaling, lysosomal degradation. Taken together, our study demonstrates members phylum contribute pathogenesis suppressing phagocytic function, which leads impaired clearance accumulation plaques.

Language: Английский

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Optimized bacterial community characterization through full-length 16S rRNA gene sequencing utilizing MinION nanopore technology

BMC Microbiology, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 16, 2024

Abstract Background Accurate identification of bacterial communities is crucial for research applications, diagnostics, and clinical interventions. Although 16S ribosomal RNA (rRNA) gene sequencing a widely employed technique taxonomic classification, it often results in misclassified or unclassified taxa. This study sought to refine the full-length rRNA protocol using MinION sequencer, focusing on V1–V9 regions. Our methodological enquiry examined several factors, including number PCR amplification cycles, choice primers Taq polymerase, specific sequence databases workflows employed. We used microbial standard comprising eight strains (five gram-positive three gram-negative) known proportions as validation control. Results Based protocol, we DNA template amplicon procedure. analysis showed that an elevated cycles introduced bias, selection polymerase primer sets significantly affected subsequent analysis. Bacterial at genus level demonstrated Pearson correlation coefficients ranging from 0.73 0.79 when assessed BugSeq, Kraken-Silva EPI2ME-16S workflows. Notably, workflow exhibited highest with standard, minimised misclassification, increased alignment accuracy. At species level, BugSeq was superior, coefficient 0.92. Conclusions These findings emphasise importance careful settings well-structured analytical framework sequencing. The robust between predicted observed abundances both levels, making these applicable across diverse contexts utility reliable pathogen identification.

Language: Английский

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Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer’s Disease Pathogenesis—From Gut Microbiota and Viruses to Brain Biofilms

Microorganisms, Journal Year: 2025, Volume and Issue: 13(1), P. 90 - 90

Published: Jan. 5, 2025

For decades, Alzheimer's Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as primary driver of disease. However, consistent failure Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores need rethink our approach AD treatment. Emerging evidence points microbial infections environmental factors in pathoetiology. Although a definitive causal link remains unestablished, collective is compelling. This review explores unconventional perspectives and emerging paradigms regarding involvement pathogenesis, emphasizing gut-brain axis, brain biofilms, oral microbiome, viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes Aβ accumulation, signaling pathways. Viral like Herpes Simplex Virus Type 1 (HSV-1) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead by modulating host processes immune system. peptide's antimicrobial function response infection might inadvertently promote AD. We discuss potential microbiome-based promising strategies for managing potentially preventing progression. Fecal transplantation (FMT) restores balance, reduces improves cognition preclinical models. Probiotics prebiotics reduce neuroinflammation plaques, while antiviral targeting HSV-1 vaccines shingles vaccine mitigate pathology. Developing effective treatments requires standardized methods identify measure patients, enabling personalized address individual contributions pathogenesis. Further needed clarify interactions between microbes Aβ, explore bacterial interplay, understand their broader effects translate these insights into clinical interventions.

Language: Английский

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Gut microbiota in Alzheimer’s disease: Understanding molecular pathways and potential therapeutic perspectives

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: 104, P. 102659 - 102659

Published: Jan. 10, 2025

Language: Английский

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