A Hierarchical Mechanotransduction System: From Macro to Micro DOI Creative Commons
Rong Cao,

Huimin Tian,

Yan Tian

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 11(11)

Published: Dec. 25, 2023

Mechanotransduction is a strictly regulated process whereby mechanical stimuli, including forces and properties, are sensed translated into biochemical signals. Increasing data demonstrate that mechanotransduction crucial for regulating macroscopic microscopic dynamics functionalities. However, the actions mechanisms of across multiple hierarchies, from molecules, subcellular structures, cells, tissues/organs, to whole-body level, have not been yet comprehensively documented. Herein, biological roles operational macro micro revisited, with focus on orchestrations diverse hierarchies. The implications, applications, challenges in human diseases also summarized discussed. Together, this knowledge hierarchical perspective has potential refresh insights regulation disease pathogenesis therapy, ultimately revolutionize prevention, diagnosis, treatment diseases.

Language: Английский

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

30
Motile cilia modulate neuronal and astroglial activity in the zebrafish larval brain DOI Creative Commons
Percival P. D’Gama, Inyoung Jeong, Andreas Moe Nygård

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(1), P. 115195 - 115195

Published: Jan. 1, 2025

Language: Английский

Citations

2
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

40
Transcranial Magneto-Acoustic Stimulation Attenuates Synaptic Plasticity Impairment through the Activation of Piezo1 in Alzheimer’s Disease Mouse Model DOI Creative Commons
Fangxuan Chu,

Ruxin Tan,

Xin Wang

et al.

Research, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

The neuropathological features of Alzheimer's disease include amyloid plaques. Rapidly emerging evidence suggests that Piezo1, a mechanosensitive cation channel, plays critical role in transforming ultrasound-related mechanical stimuli through its trimeric propeller-like structure, but the importance Piezo1-mediated mechanotransduction brain functions is less appreciated. However, apart from stimulation, Piezo1 channels are strongly modulated by voltage. We assume may play converting and electrical signals, which could induce phagocytosis degradation Aβ, combined effect stimulation superior to single stimulation. Hence, we design transcranial magneto-acoustic (TMAS) system, based on ultrasound (TUS) within magnetic field combines coupling electric force ultrasound, applied it test above hypothesis 5xFAD mice. Behavioral tests, vivo electrophysiological recordings, Golgi-Cox staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, RNA sequencing, cerebral blood flow monitoring were used assess whether TMAS can alleviate symptoms AD mouse model activating Piezo1. treatment enhanced autophagy promote β-amyloid activation microglial alleviated neuroinflammation, synaptic plasticity impairment, neural oscillation abnormalities mice, showing stronger than ultrasound. inhibition with an antagonist, GsMTx-4, prevented these beneficial effects TMAS. This research indicates transform TMAS-related into biochemical signals identifies favorable mice mediated

Language: Английский

Citations

30
Extracellular ATP/adenosine dynamics in the brain and its role in health and disease DOI Creative Commons
Eiji Shigetomi, K Sakai, Schuichi Koizumi

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 18, 2024

Extracellular ATP and adenosine are neuromodulators that regulate numerous neuronal functions in the brain. Neuronal activity brain insults such as ischemic traumatic injury upregulate these neuromodulators, which exert their effects by activating purinergic receptors. In addition, extracellular ATP/adenosine signaling plays a pivotal role pathogenesis of neurological diseases. Virtually every cell type contributes to elevation ATP/adenosine, various mechanisms underlying this increase have been proposed. is thought be mainly produced via degradation ATP. However, also released from neurons glia Therefore, regulation physiological pathophysiological conditions likely far more complex than previously thought. To elucidate levels, accurate methods assessing spatiotemporal dynamics needed. Several novel techniques for acquiring information on including fluorescent sensors, developed started reveal release, uptake ATP/adenosine. Here, we review analyzing well current state knowledge We focus used cooperatively produce activity-dependent its significance

Language: Английский

Citations

11
Progressive Irreversible Proprioceptive Piezo2 Channelopathy-Induced Lost Forced Peripheral Oscillatory Synchronization to the Hippocampal Oscillator May Explain the Onset of Amyotrophic Lateral Sclerosis Pathomechanism DOI Creative Commons
Balázs Sonkodi

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 492 - 492

Published: March 12, 2024

Amyotrophic lateral sclerosis (ALS) is a mysterious lethal multisystem neurodegenerative disease that gradually leads to the progressive loss of motor neurons. A recent non-contact dying-back injury mechanism theory for ALS proposed primary damage an acquired irreversible intrafusal proprioceptive terminal Piezo2 channelopathy with underlying genetic and environmental risk factors. Underpinning this excessively prolonged mechanotransduction under allostasis may induce dysfunctionality in mitochondria, leading channelopathy. This microinjury suggested provide one gateway from physiology pathophysiology. The chronic, but not irreversible, form implicated many diseases unknown etiology. Dry eye them where replenishing synthetic proteoglycans promote nerve regeneration. Syndecans, especially syndecan-3, are as first critical link hierarchical ordered depletory pathomechanism proton-collecting/distributing antennas; hence, they play role onset. Even more importantly, shedding or charge-altering variants Syndecan-3 contribute channelopathy-induced disruption Piezo2-initiated proton-based ultrafast long-range signaling through VGLUT1 VGLUT2. Thus, these alterations only cause hippocampus conscious proprioception, could disrupt feedback motoneurons. Correspondingly, inert signaled skeletal system coming light be progressively lost ALS. In addition, functional MyoD family inhibitor proteins, auxiliary subunits Piezo2, theorized channelopathy, explain how microinjured ion channels evolve principal transcription activators.

Language: Английский

Citations

9
Calcium‐Dependent Signaling in Astrocytes: Downstream Mechanisms and Implications for Cognition DOI
Alexandra Veiga, Daniela Sofia Abreu, José Duarte Dias

et al.

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(2)

Published: Feb. 1, 2025

Astrocytes are glial cells recognized for their diverse roles in regulating brain circuit structure and function. They can sense adapt to changes the microenvironment due unique structural biochemical properties. A key aspect of astrocytic function involves calcium (Ca2+)-dependent signaling, which serves as a fundamental mechanism interactions with neurons other brain. However, while significant progress has been made understanding spatio-temporal properties Ca2+ signals, downstream molecular pathways exact mechanisms through astrocytes decode these signals regulate homeostatic physiological processes remain poorly understood. To address this topic, we review here available literature on sources intracellular Ca2+, well its signaling pathways. We well-studied Ca2+-dependent exocytosis but draw attention additional that less understood are, most likely, highly influential many cellular functions. Finally, how is thought underlie neuron-astrocyte regions involved cognitive processing.

Language: Английский

Citations

1
Mechanosensitive brain tumor cells construct blood-tumor barrier to mask chemosensitivity DOI Creative Commons
Xin Chen,

Ali Momin,

Siyi Wanggou

et al.

Neuron, Journal Year: 2022, Volume and Issue: 111(1), P. 30 - 48.e14

Published: Nov. 1, 2022

Language: Английский

Citations

31
Piezo1 agonist restores meningeal lymphatic vessels, drainage, and brain-CSF perfusion in craniosynostosis and aged mice DOI Creative Commons

Matt J. Matrongolo,

Phillip S. Ang,

Junbing Wu

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 134(4)

Published: Nov. 2, 2023

Skull development coincides with the onset of cerebrospinal fluid (CSF) circulation, brain-CSF perfusion, and meningeal lymphangiogenesis, processes essential for brain waste clearance. How these are affected by craniofacial disorders such as craniosynostosis poorly understood. We report that raised intracranial pressure diminished CSF flow in mouse models associates pathological changes to lymphatic vessels affect their sprouting, expansion, long-term maintenance. also show affects circulatory pathways perfusion into brain. Further, exacerbates amyloid pathology plaque buildup Twist1+/-:5xFAD transgenic Alzheimer's disease models. Treating mice Yoda1, a small molecule agonist Piezo1, reduces improves flow, addition restoring drainage deep cervical lymph nodes, perfusion. Leveraging findings, we Yoda1 treatments aged reduced turnover improve networks, drainage, Our results suggest provides mechanical force facilitate growth Additionally, applying conditions and/or seen or ageing, is possible therapeutic option help restore networks

Language: Английский

Citations

22
Mechanosensitive Piezo1 channel in physiology and pathophysiology of the central nervous system DOI Creative Commons
Boyi Zong,

Fengzhi Yu,

Xiaoyou Zhang

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 90, P. 102026 - 102026

Published: July 31, 2023

Since the discovery of mechanosensitive Piezo1 channel in 2010, there has been a significant amount research conducted to explore its regulatory role physiology and pathology various organ systems. Recently, growing body compelling evidence emerged linking activity health disease central nervous system. However, exact mechanisms underlying these associations remain inadequately comprehended. This review systematically summarizes current on implications for system mechanobiology, retrospects results demonstrating cell types within system, including neural stem cells, neurons, oligodendrocytes, microglia, astrocytes, brain endothelial cells. Furthermore, discusses understanding involvement disorders, such as Alzheimer's disease, multiple sclerosis, glaucoma, stroke, glioma.

Language: Английский

Citations

19