Biochemistry (Moscow), Год журнала: 2024, Номер 89(12-13), С. 2107 - 2132
Опубликована: Дек. 1, 2024
Язык: Английский
Ageing Research Reviews, Год журнала: 2024, Номер unknown, С. 102515 - 102515
Опубликована: Сен. 1, 2024
Язык: Английский
Процитировано
8
Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)
Опубликована: Янв. 30, 2025
Abstract Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise possibility that pathogenic alpha-synuclein (⍺-syn) might develop GI tract subsequently spread to susceptible brain regions. The cellular mechanistic origins ⍺-syn propagation disease are under intense investigation. Experimental LBD models have implicated important contributions from intrinsic gut microbiome, intestinal immune system, environmental toxicants, acting as triggers modifiers pathologies. Here, we review primary clinical observations link dysfunctions LBDs. We first provide an overview anatomy repertoire relevant for disease, with a focus on luminal-sensing cells epithelium including enteroendocrine express make direct contact nerves. describe interactions within resident microbes exogenous how these may directly contribute pathology along related metabolic immunological responses. Finally, critical knowledge gaps field highlighted, focusing pivotal questions remain some 200 years after dysfunction predict better understanding pathophysiologies influence risk progression will accelerate discoveries lead deeper overall potential therapeutic strategies targeting gut-brain axis delay, arrest, or prevent progression.
Язык: Английский
Процитировано
1
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2695 - 2695
Опубликована: Март 17, 2025
Biofilm-associated amyloid proteins have emerged as significant contributors to the progression of neurodegenerative diseases, representing a complex intersection microorganisms and human health. The cross-beta sheet structure characteristic amyloids produced by gut-colonizing bacteria remains intact, crucial for resilience biofilms. These exacerbate disorders such Alzheimer’s Parkinson’s cross-seeding amyloidogenic like amyloid-beta α-synuclein, accelerating their misfolding aggregation. Despite molecular chaperones heat shock maintaining protein homeostasis, bacterial can overwhelm them, worsening neuronal damage. Genetic variations in chaperone genes further influence amyloidogenesis neurodegeneration. Persistent infections inflammation compromise blood-brain barrier, allowing inflammatory molecules enter brain, perpetuating cycle gut-brain axis underscores impact dysbiosis gut microbiota on brain function, potentially contributing enhancement biofilm antibiotic resistance functional fibrils complicates treatment landscape. interplay among systems, microbial amyloids, diseases urgent need advanced strategies targeting these pathways attenuate disease progression. Understanding processes that relate biofilm-associated onset neurological is critical diagnosing developing novel strategies.
Язык: Английский
Процитировано
1
Gut Microbes, Год журнала: 2024, Номер 16(1)
Опубликована: Ноя. 10, 2024
Deciphering the molecular communications along gut-brain axis can help in understanding pathophysiology of neurodegenerative diseases and exploiting gut microbiome for therapeutics. However, microbes their metabolites have a multifaceted role mediating both brain physiology pathology. There is lack how when this tipped what are those contributing factors, at local (gut) distal (neuronal) levels, that drive imbalance. Here we reviewed its context summarized different factors such as gut-microbial diversity, metabolites, native immune system integrity epithelial blood-brain barriers interconnected collectively define involvement gut-microbiome pathologies. It also underlines need multidisciplinary tools animal models to simultaneously reflect on many these better correlate with clinical observations data obtained from human biopsies fecal samples. Harnessing will herald paradigm shift medicine aging, emphasizing significance broader spectrum health disease.
Язык: Английский
Процитировано
4
Journal of Neuroscience Research, Год журнала: 2025, Номер 103(1)
Опубликована: Янв. 1, 2025
Parkinson's Disease (PD) is a neurodegenerative disorder marked by the depletion of dopaminergic neurons. Recent studies highlight gut-liver-brain (GLB) axis and its role in PD pathogenesis. The GLB forms dynamic network facilitating bidirectional communication between gastrointestinal tract, liver, central nervous system. Dysregulation within this axis, encompassing gut dysbiosis microbial metabolites, emerging as critical factor influencing progression. Our understanding was traditionally centered on processes brain. However, examining through lens provides new insights. This review comprehensive analysis such short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), kynurenine, serotonin, bile acids, indoles, dopamine, which are integral to pathogenesis modulation axis. extensive research included literature database searches utilizing resources gutMGene gutMDisorder. These databases have been instrumental identifying specific microbes their shedding light intricate relationship PD. consolidates existing knowledge underscores potential for targeted therapeutic interventions based components, offer avenues future treatment strategies. While not novel concept, first focus specifically PD, highlighting importance integrating liver metabolites players puzzle.
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Янв. 15, 2025
Abstract Gut bacteria have emerged as silent drivers in the pathology of Alzheimer’s disease (AD). They also make amyloids with structure analogue to pathological and potential cross-seed propagate a prion-like manner. AD is characterised by accumulation mature extracellular Amyloid-β (Aβ) plaques which are surrounded inflammatory microglia. We report that exposure interspecies microbial FapC (fimbriae) CsgA (curli) from opportunistic gut pathogens Pseudomonas aeruginosa Escherichia coli hyperactivates microglia against Aβ fibrils. Microbial fibrils converge phagocytic compartments through subsequent internalization, not observed alone. This convergence promotes pro-inflammatory defective proteome similar those brains. The resulting clusters develop pro-inflammatory, indigestible interactome eventually regurgitated, inducing progressive degeneration bystander neurons ultimately leading cognitive decline. Collectively, these findings provide compelling evidence can trigger microglia-driven neuroinflammation.
Язык: Английский
Процитировано
0
Gut Microbes, Год журнала: 2025, Номер 17(1)
Опубликована: Фев. 3, 2025
Human microbiota form a biofilm with substantial consequences for health and disease. Numerous studies have indicated that microbial communities produce functional amyloids as part of their extracellular scaffolds. The overlooked interplay between bacterial the host may detrimental host, including neurodegeneration. This work gives an overview biofilm-associated expressed by gut potential role in It discusses proteins (BAPs) microbiota, maps amyloidogenic domains these proteins, analyzes presence bap genes within accessory genomes linked transposable elements. Furthermore, evidence supporting existence are presented. Finally, it explores interactions BAPs α-synuclein, extending literature on amyloid cross-kingdom interactions. Based findings, this study propose BAP act transmissible catalysts, facilitating misfolding, accumulation, spread α-synuclein aggregates. review contributes to understanding complex among elements, which is crucial developing novel therapeutic approaches combat microbiota-related diseases improve overall outcomes.
Язык: Английский
Процитировано
0
Current Opinion in Neurology, Год журнала: 2025, Номер unknown
Опубликована: Фев. 7, 2025
Purpose of review The present aims to provide an overview the existing understanding role gut microbiome in Alzheimer's disease pathophysiology. Recent findings research has highlighted significant pathogenesis via gut-brain axis. However, precise mechanisms by which and its microbial metabolites influence brain function are not clearly understood. Various factors, such as diet, drugs, lifestyle, stress, infections can provoke imbalance homeostasis, known dysbiosis. This dysbiosis impacts intestinal blood-brain barrier permeability, elevating pro-inflammatory cytokines contributing neurodegeneration. Moreover, generates neurotransmitters, amyloids, neurotoxins, metabolites, may play a systemic inflammation disruption physiological barriers. Summary In past decade, advancements analysis technologies bioinformatics have significantly enhanced our disease. plays pivotal regulatory progression disease, closely interacts with pathogenesis, encompassing inflammation, amyloidosis, neurodegeneration, tauopathy, co-pathologies.
Язык: Английский
Процитировано
0
Translational Medicine of Aging, Год журнала: 2025, Номер 9, С. 41 - 48
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Molecular Aspects of Medicine, Год журнала: 2025, Номер 103, С. 101351 - 101351
Опубликована: Март 1, 2025
The amyloid state of proteins occurs in many different contexts Nature and modern society, ranging from the pathological kind (neurodegenerative diseases amyloidosis) via man-made forms (food processing - to a much smaller extent protein biologics) functional versions (bacterial biofilm, peptide hormones signal transmission). These classes all come together human body which endogenously produces amyloidogenic able form (PaHA), hosts microbiome continuously makes bacterial (FuBA) ingests food can contain amyloid. This have grave consequences, given that PaHA spread throughout "hand-me-down" fashion cell through small fragments, kick-start growth new wherever they encounter monomeric precursors. Amyloid also self- cross-seed across dissimilar sequences. While it is very unlikely ingested plays role this crosstalk, FuBA-PaHA interactions are increasingly implicated vivo propagation. We now position understand structural bioinformatic basis for cross-talk, thanks recently obtained atomic-level structures two major FuBAs CsgA (E. coli) FapC (Pseudomonas). there reports homology-driven heterotypic between PaHA, proteome does not harbor significant homology FapC. Yet we others uncovered cross-stimulation (and some cases inhibition) FuBA both vitro vivo, here rationalize based on structure sequence. important consequences transmission development neurodegenerative diseases, least because into contact gut-brain interface, recurrent infections with microbes potentially even invasive biofilm brain. Whether first interact gut or brain, stimulate block each other's aggregation as well trigger inflammatory responses. may affect amyloidogenesis other ways, e.g. their own chaperones recognize show experimentally computationally. Heterotypic within vital part phenomenon constitute vibrant exciting frontier future research.
Язык: Английский
Процитировано
0