TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction DOI Creative Commons
Xiaoxue Zhang,

Jichen Shao,

Caixue Wang

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 114014 - 114014

Published: April 1, 2024

The transmembrane channel-like (TMC) protein family comprises eight members, with TMC1 and TMC2 being extensively studied. This study demonstrates substantial co-expression of TMC7 the mechanosensitive channel Piezo2 in somatosensory neurons. Genetic deletion primary sensory ganglia neurons vivo enhances sensitivity both physiological pathological mechanosensory transduction. leads to an increase proportion rapidly adapting (RA) currents conducted by dorsal root ganglion (DRG) accelerates RA deactivation kinetics. In HEK293 cells expressing proteins, significantly suppresses current amplitudes co-expressed Piezo2. Our findings reveal that exhibit physical interactions, proteins also physically interact cytoskeletal β-actin. We hypothesize functions as inhibitory modulator DRG neurons, either through direct inhibition or disrupting transmission mechanical forces from cytoskeleton channel.

Language: Английский

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases DOI Creative Commons
Jian Sheng Loh, Wen Qi Mak, Li Tan

et al.

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

Published: Feb. 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

Language: Английский

Citations

237
Ultrasound as a versatile tool for short- and long-term improvement and monitoring of brain function DOI Creative Commons
Daniel G. Blackmore, Daniel Razansky, Jürgen Götz

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(8), P. 1174 - 1190

Published: March 13, 2023

Language: Английский

Citations

45
Mechanisms of mechanotransduction and physiological roles of PIEZO channels DOI
Bailong Xiao

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 9, 2024

Language: Английский

Citations

28
Brain clearance of protein aggregates: a close-up on astrocytes DOI Creative Commons
Veronica Giusti, G Kaur, Elena Giusto

et al.

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: Jan. 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.

Language: Английский

Citations

22
Neuroinflammation in Alzheimer disease DOI
Wiesje M. van der Flier, Wiesje M. van der Flier,

Frank Jessen

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Language: Английский

Citations

18
Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression DOI Creative Commons
Yi‐Cheng Zhu,

Jiaoshun Chen,

Chen Chen

et al.

Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 23, 2025

The tumor microenvironment functions as a dynamic and intricate ecosystem, comprising diverse array of cellular non-cellular components that precisely orchestrate pivotal behaviors, including invasion, metastasis, drug resistance. While unraveling the interplay between behaviors represents tremendous challenge, recent research illuminates crucial biological phenomenon known mechanotransduction. Within microenvironment, mechanical cues like tensile stress, shear stiffness play role by activating mechanosensitive effectors such PIEZO proteins, integrins, Yes-associated protein. This activation initiates cascades intrinsic signaling pathways, effectively linking physical properties tissues to their physiological pathophysiological processes morphogenesis, regeneration, immunity. mechanistic insight offers novel perspective on how within impact behaviors. intricacies are yet be fully elucidated, it exhibits distinct attributes from non-malignant tissues, elevated solid stresses, interstitial hypertension, augmented matrix stiffness, enhanced viscoelasticity. These traits exert notable influences progression treatment responses, enriching our comprehension multifaceted nature microenvironment. Through this innovative review, we aim provide new lens decipher contexts, broadening knowledge these factors promote or inhibit thus offering valuable insights identify potential targets for anti-tumor strategies.

Language: Английский

Citations

2
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 DOI Creative Commons
Philippa Malko,

Xiaoling Jia,

Ian Wood

et al.

Glia, Journal Year: 2022, Volume and Issue: 71(4), P. 848 - 865

Published: Nov. 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.

Language: Английский

Citations

44
Mechanics in the nervous system: From development to disease DOI Creative Commons
Eva K. Pillai, Kristian Franze

Neuron, Journal Year: 2023, Volume and Issue: 112(3), P. 342 - 361

Published: Nov. 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.

Language: Английский

Citations

38
Noteworthy perspectives on microglia in neuropsychiatric disorders DOI Creative Commons
Hongrui Zhu,

Ao Guan,

Jiayuan Liu

et al.

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Oct. 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.

Language: Английский

Citations

37
Induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation DOI
Debosmita Sardar, Yi-Ting Cheng, Junsung Woo

et al.

Science, Journal Year: 2023, Volume and Issue: 380(6650)

Published: June 15, 2023

Neuronal activity drives alterations in gene expression within neurons, yet how it directs transcriptional and epigenomic changes neighboring astrocytes functioning circuits is unknown. We found that neuronal induces widespread up-regulation down-regulation astrocytes, highlighted by the identification of

Language: Английский

Citations

34