Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 140, P. 1 - 2
Published: Sept. 7, 2022
Language: Английский
Pharmacological Research, Journal Year: 2023, Volume and Issue: 197, P. 106975 - 106975
Published: Oct. 29, 2023
Nicotinic acetylcholine receptors (nAChRs) belong to a superfamily of cys-loop characterized by the assembly five subunits into multi-protein channel complex. Ligand binding nAChRs activates rapid allosteric transitions receptor leading opening and ion flux in neuronal non-neuronal cell. Thus, while ionotropic properties are well recognized, less is known about ligand-mediated intracellular "metabotropic" signaling nAChRs. Studies neural non-neural cells confirm that metabotropic responses observable following ligand binding. In this review we summarize evidence on existence homopentameric α7 various cell types. We explore how coordinated calcium entry through release from nearby stores gives rise important for modulation cytoskeletal motility growth. Amino acid residues for, protein within human nAChR support engagement including heterotrimeric G proteins immune cells. Understanding dual likely essential advancing drug development other mechanistic treatments disease.
Language: Английский
Citations
12
Future Virology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15
Published: March 21, 2025
Language: Английский
Citations
0
Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(5), P. 1244 - 1257
Published: April 16, 2024
Current treatments for epilepsy can only manage the symptoms of condition but cannot alter initial onset or halt progression disease. Consequently, it is crucial to identify drugs that target novel cellular and molecular mechanisms action. Increasing evidence suggests axon guidance molecules play a role in structural functional modifications neural networks dysregulation these associated with susceptibility. In this review, we discuss essential neuronal activity patients as well impact on synaptic plasticity brain tissue remodeling. Furthermore, examine relationship between neuroinflammation, changes specific regions contribute development epilepsy. Ample indicates molecules, including semaphorins ephrins, fundamental guiding growth establishment connections. Deviations their expression function disrupt connections, ultimately leading epileptic seizures. The remodeling significant characteristic epilepsy, playing dynamic reorganization circuits. This, turn, affects synapse formation elimination. Dysregulation upset delicate balance excitation inhibition within network, thereby increasing risk overexcitation Inflammatory signals regulate thus influencing axonal growth, orientation, plasticity. neuroinflammation intensify dysfunction occurrence This review delves into pathogenicity offering valuable reference exploration therapeutic targets presenting fresh perspective treatment strategies condition.
Language: Английский
Citations
3
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 12, 2025
Axons experience strong mechanical forces due to animal movement. While these serve as sensory cues in mechanosensory neurons, their impact on other neuron types remains poorly defined. Here, we uncover signaling that controls an axonal cytoskeletal response external physiological and plays a key role integrity. Live imaging of microtubules at single-polymer resolution C. elegans motor reveals local oscillatory movements fine-tune polymer positioning. Combining cell-specific chemogenetic silencing with targeted degradation alleles distinguish neuron-intrinsic from extrinsic regulators movements, find they are driven by muscle contractions require the mechanosensitive protein Talin, small GTPase RhoA, actomyosin activity axon. Genetic perturbation axon's ability buffer tension disrupting spectrin-based membrane-associated skeleton leads RhoA hyperactivation, relocalization foci microtubule ends, converts oscillations into processive bidirectional movements. This results large gaps between microtubules, coverage axon leading its breakage degeneration. Notably, hyperpolarizing or degrading components mechanotransduction pathway rescues defects spectrin-deficient axons. These identify mechanisms highlight importance force-buffering for
Language: Английский
Citations
0
Published: Jan. 1, 2025
Language: Английский
Citations
0
Biological Chemistry, Journal Year: 2023, Volume and Issue: 405(1), P. 67 - 77
Published: Sept. 7, 2023
Microtubules are highly polar structures and characterized by high anisotropy stiffness. In neurons, they play a key role in the directional transport of vesicles organelles. neuronal projections called axons, form parallel bundles, mostly oriented with plus-end towards axonal termination. Their physico-chemical properties have recently attracted attention as potential candidate sensing, processing transducing physical signals generated mechanical forces. Here, we discuss main evidence supporting microtubules signal hub for axon growth response to traction force. Applying tension appears stabilize microtubules, which, turn, coordinate modulation transport, local translation their cross-talk. We speculate on possible mechanisms modulating microtubule dynamics under tension, based collected non-neuronal cell types. However, fundamental question causal relationship between these is still elusive because mechano-sensitive element this chain has not yet been identified.
Language: Английский
Citations
9
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: July 16, 2024
Abstract Tension propagates in lipid bilayers over hundreds of microns within milliseconds, precluding the formation tension gradients. Nevertheless, plasma membrane gradients have been evidenced migrating cells and along axons. Here, using a fluorescent probe, we show that exist all adherent cells, whether they migrate or not. Non-adhering do not display We further branched actin increases tension, while membrane-to-cortex attachments facilitate its propagation. is lowest at edge adhesion sites highest protrusions, setting boundaries By providing quantitative mechanistic basis behind organization gradients, our work explains how are actively sustained cells.
Language: Английский
Citations
1
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: May 23, 2024
ABSTRACT Axonal outgrowth, cell crawling, and cytokinesis utilize actomyosin, microtubule-based motors, cytoskeletal dynamics, substrate adhesions to produce traction forces bulk cellular motion. While it has long been appreciated that growth cones resemble crawling cells the mechanisms drive help power they are typically viewed as unique processes. To better understand relationship between these modes of motility, here, we developed a unified active fluid model cytokinesis, amoeboid migration, mesenchymal neuronal axonal outgrowth in terms flow, adhesions, viscosity, force generation. Using numerical modeling, fit subcellular velocity profiles motions structures docked organelles from previously published studies infer underlying patterns generation adhesion. Our results indicate that, during there is primary converge zone at cleavage furrow drives flow towards it; symmetric across cell, result, stationary. In mesenchymal, amoeboid, site shifts, differences adhesion front back crawling. During migration convergence lies within cone, which actin retrograde P-domain anterograde shaft. They differ body weakly attached thus moves forward same axon. contrast, strongly adheres remains stationary, resulting decrease away cone. The simplicity with can be modeled by varying coefficients simple suggests deep connection them.
Language: Английский
Citations
0
Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12
Published: Oct. 17, 2024
While the structural organization and molecular biology of neurons are well characterized, physical process axonal elongation remains elusive. The classic view posited occurs through deposition cytoskeletal elements in growth cone at tip a stationary array microtubules. Yet, recent studies reveal microtubules docked organelles flow forward bulk elongating axons
Language: Английский
Citations
0
Langmuir, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 9, 2024
The use of self-assembling peptide hydrogels in the treatment spinal cord and brain injuries, especially when combined with adult neural stem cells, has shown great potential. To advance tissue engineering, it is essential to understand effect mechanochemical signaling on cellular differentiation. elucidation molecular interactions at level neuronal membrane still represents a promising area investigation for many drug delivery engineering applications. An innovative dynamics framework been introduced investigate SAP fibrils different charges lipid domain dynamics. Such enables silico exploration biomimetic properties other polymeric biomaterials
Language: Английский
Citations
0