Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Фев. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Язык: Английский

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Microglial Piezo1 senses Aβ fibril stiffness to restrict Alzheimer’s disease

Neuron, Год журнала: 2022, Номер 111(1), С. 15 - 29.e8

Опубликована: Ноя. 10, 2022

Язык: Английский

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Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Авг. 5, 2023

Microglia are the resident innate immune cells in brain with a major role orchestrating responses. They also provide frontline of host defense central nervous system (CNS) through their active phagocytic capability. Being professional phagocyte, microglia participate and autophagic clearance cellular waste debris as well toxic protein aggregates, which relies on optimal lysosomal acidification function. Defective microglial leads to impaired functions result perpetuation neuroinflammation progression neurodegeneration. Reacidification lysosomes has been shown reverse neurodegenerative pathology Alzheimer's disease. In this review, we summarize key factors mechanisms contributing impairment associated dysfunction microglia, how these defects contribute We further discuss techniques monitor pH therapeutic agents that can reacidify under disease conditions. Finally, propose future directions investigate lysosome-mitochondria crosstalk neuron-glia interaction for more comprehensive understanding its broader CNS physiological pathological implications.

Язык: Английский

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Ultrasound as a versatile tool for short- and long-term improvement and monitoring of brain function

Neuron, Год журнала: 2023, Номер 111(8), С. 1174 - 1190

Опубликована: Март 13, 2023

Язык: Английский

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Mechanisms of mechanotransduction and physiological roles of PIEZO channels

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

Язык: Английский

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Brain clearance of protein aggregates: a close-up on astrocytes

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Янв. 16, 2024

Abstract Protein misfolding and accumulation defines a prevailing feature of many neurodegenerative disorders, finally resulting in the formation toxic intra- extracellular aggregates. Intracellular aggregates can enter space be subsequently transferred among different cell types, thus spreading between connected brain districts. Although microglia perform predominant role removal aggregated proteins, mounting evidence suggests that astrocytes actively contribute to clearing process. However, molecular mechanisms used by remove misfolded proteins are still largely unknown. Here we first provide brief overview progressive transition from soluble monomers insoluble fibrils characterizes amyloid referring α-Synuclein Tau as archetypical examples. We then highlight at basis astrocyte-mediated clearance with focus on their potential ability recognize, collect, internalize digest protein Finally, explore targeting future therapeutic approach for treatment disorders characterized accumulation.

Язык: Английский

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Reactive gliosis in traumatic brain injury: a comprehensive review

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Фев. 28, 2024

Traumatic brain injury (TBI) is one of the most common pathological conditions impacting central nervous system (CNS). A neurological deficit associated with TBI results from a complex pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or development edema. The critical components contributing to CNS response, damage control, and regeneration after are glial cells–in reaction tissue damage, their activation, hypertrophy, proliferation occur, followed by formation scar. scar creates barrier in damaged helps protect acute phase post-injury. However, this process prevents complete recovery late/chronic producing permanent scarring, which significantly impacts function. Various types participate formation, but mostly attributed reactive astrocytes microglia, play important roles several pathologies. Novel technologies whole-genome transcriptomic epigenomic analyses, unbiased proteomics, show that both microglia represent groups heterogenic subpopulations different genomic functional characteristics, responsible for role neurodegeneration, neuroprotection regeneration. Depending on representation distinct glia subpopulations, as well regenerative processes delayed neurodegeneration may thus differ nearby remote areas structures. This review summarizes process, where resultant effect severity-, region- time-dependent determined model distance explored area lesion site. Here, we also discuss findings concerning intercellular signaling, long-term possibilities novel therapeutical approaches. We believe comprehensive study an emphasis cells, involved post-injury processes, be helpful further research decisive factor when choosing model.

Язык: Английский

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Piezo1 channel‐mediated Ca²⁺ signaling inhibits lipopolysaccharide‐induced activation of the NF‐κB inflammatory signaling pathway and generation of TNF‐α and IL‐6 in microglial cells

Glia, Год журнала: 2022, Номер 71(4), С. 848 - 865

Опубликована: Ноя. 29, 2022

Microglial cells are crucial in maintaining central nervous system (CNS) homeostasis and mediating CNS disease pathogenesis. Increasing evidence supports that alterations the mechanical properties of microenvironments influence glial cell phenotypes, but mechanisms regulating microglial function remain elusive. Here, we examined mechanosensitive Piezo1 channel cells, particularly, how activation regulates pro-inflammatory production cytokines, using BV2 primary cells. expression was detected both at mRNA protein levels. Application activator Yoda1 induced Ca2+ flux to increase intracellular concentration reduced by treatment with ruthenium red, a inhibitor, or Piezo1-specific siRNA, supporting functions as surface -permeable channel. Priming lipopolysaccharide (LPS) TNF-α IL-6, which were inhibited Yoda1. Furthermore, LPS priming ERK, p38 MAPKs, NF-κB. LPS-induced NF-κB, not ERK p38, Yoda1-induced inhibition blunted siRNA-mediated depletion and, furthermore, BAPTA-AM prevent increase. Collectively, our results support downregulates especially initiating signaling inhibit NF-κB inflammatory pathway. These findings reveal previously unrecognized mechanism function, raising an interesting perspective on targeting this molecular alleviate neuroinflammation associated pathologies.

Язык: Английский

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Noteworthy perspectives on microglia in neuropsychiatric disorders

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Окт. 4, 2023

Abstract Microglia are so versatile that they not only provide immune surveillance for central nervous system, but participate in neural circuitry development, brain blood vessels formation, blood–brain barrier architecture, and intriguingly, the regulation of emotions behaviors. have a profound impact on neuronal survival, wiring synaptic plasticity. As professional phagocytic cells brain, remove dead cell debris neurotoxic agents via an elaborate mechanism. The functional profile microglia varies considerately depending age, gender, disease context other internal or external environmental factors. Numerous studies demonstrated pivotal involvement neuropsychiatric disorders, including negative affection, social deficit, compulsive behavior, fear memory, pain symptoms associated with major depression disorder, anxiety autism spectrum disorder schizophrenia. In this review, we summarized latest discoveries regarding microglial ontogeny, subtypes state spectrum, biological functions mechanistic underpinnings emotional behavioral disorders. Furthermore, highlight potential microglia-targeted therapies propose outstanding questions to be addressed future research human microglia.

Язык: Английский

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Mechanics in the nervous system: From development to disease

Neuron, Год журнала: 2023, Номер 112(3), С. 342 - 361

Опубликована: Ноя. 14, 2023

Physical forces are ubiquitous in biological processes across scales and diverse contexts. This review highlights the significance of mechanical nervous system development, homeostasis, disease. We provide an overview signals present delve into mechanotransduction mechanisms translating these cues biochemical signals. During regulate a plethora processes, including cell proliferation, differentiation, migration, network formation, cortex folding. Forces then continue exerting their influence on physiological such as neuronal activity, glial function, interplay between different types. Notably, changes tissue mechanics manifest neurodegenerative diseases brain tumors, potentially offering new diagnostic therapeutic target opportunities. Understanding role cellular physiology pathology adds facet to neurobiology, shedding light many that remain incompletely understood.

Язык: Английский

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