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Search Results (319)

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57 pages, 4553 KB  
Review
Properties and Pharmacology of Scorpion Toxins and Their Biotechnological Potential in Agriculture and Medicine
by Cháriston André Dal Belo, Stephen Hyslop and Célia Regina Carlini
Toxins 2025, 17(10), 497; https://doi.org/10.3390/toxins17100497 - 7 Oct 2025
Abstract
Scorpion venoms contain a wide range of toxins that interact with a variety of target molecules (ion channels, receptors and enzymes) associated with synaptic transmission, action potential propagation, cardiac function, hemostasis and other physiological systems. Scorpion toxins are also active towards bacteria, viruses, [...] Read more.
Scorpion venoms contain a wide range of toxins that interact with a variety of target molecules (ion channels, receptors and enzymes) associated with synaptic transmission, action potential propagation, cardiac function, hemostasis and other physiological systems. Scorpion toxins are also active towards bacteria, viruses, fungi and parasites. Such interactions make scorpion toxins useful lead molecules for developing compounds with biotechnological and therapeutic applications, and as tools for cell biology. In addition, scorpion toxins act as insectotoxins, with promising applications as insecticides. This review describes the range of scorpion toxins and discusses their usefulness for the development of insecticides and therapeutic drugs. Full article
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24 pages, 4022 KB  
Article
Dynamic Vision Sensor-Driven Spiking Neural Networks for Low-Power Event-Based Tracking and Recognition
by Boyi Feng, Rui Zhu, Yue Zhu, Yan Jin and Jiaqi Ju
Sensors 2025, 25(19), 6048; https://doi.org/10.3390/s25196048 - 1 Oct 2025
Viewed by 401
Abstract
Spiking neural networks (SNNs) have emerged as a promising model for energy-efficient, event-driven processing of asynchronous event streams from Dynamic Vision Sensors (DVSs), a class of neuromorphic image sensors with microsecond-level latency and high dynamic range. Nevertheless, challenges persist in optimising training and [...] Read more.
Spiking neural networks (SNNs) have emerged as a promising model for energy-efficient, event-driven processing of asynchronous event streams from Dynamic Vision Sensors (DVSs), a class of neuromorphic image sensors with microsecond-level latency and high dynamic range. Nevertheless, challenges persist in optimising training and effectively handling spatio-temporal complexity, which limits their potential for real-time applications on embedded sensing systems such as object tracking and recognition. Targeting this neuromorphic sensing pipeline, this paper proposes the Dynamic Tracking with Event Attention Spiking Network (DTEASN), a novel framework designed to address these challenges by employing a pure SNN architecture, bypassing conventional convolutional neural network (CNN) operations, and reducing GPU resource dependency, while tailoring the processing to DVS signal characteristics (asynchrony, sparsity, and polarity). The model incorporates two innovative, self-developed components: an event-driven multi-scale attention mechanism and a spatio-temporal event convolver, both of which significantly enhance spatio-temporal feature extraction from raw DVS events. An Event-Weighted Spiking Loss (EW-SLoss) is introduced to optimise the learning process by prioritising informative events and improving robustness to sensor noise. Additionally, a lightweight event tracking mechanism and a custom synaptic connection rule are proposed to further improve model efficiency for low-power, edge deployment. The efficacy of DTEASN is demonstrated through empirical results on event-based (DVS) object recognition and tracking benchmarks, where it outperforms conventional methods in accuracy, latency, event throughput (events/s) and spike rate (spikes/s), memory footprint, spike-efficiency (energy proxy), and overall computational efficiency under typical DVS settings. By virtue of its event-aligned, sparse computation, the framework is amenable to highly parallel neuromorphic hardware, supporting on- or near-sensor inference for embedded applications. Full article
(This article belongs to the Section Intelligent Sensors)
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26 pages, 6743 KB  
Article
Matrix-Guided Vascular-like Cord Formation by MRC-5 Lung Fibroblasts: Evidence of Structural and Transcriptional Plasticity
by Nikoleta F. Theodoroula, Alexandros Giannopoulos-Dimitriou, Aikaterini Saiti, Aliki Papadimitriou-Tsantarliotou, Androulla N. Miliotou, Giannis Vatsellas, Yiannis Sarigiannis, Eleftheria Galatou, Christos Petrou, Dimitrios G. Fatouros and Ioannis S. Vizirianakis
Cells 2025, 14(19), 1519; https://doi.org/10.3390/cells14191519 - 29 Sep 2025
Viewed by 661
Abstract
The role of mesenchymal-to-endothelial transition in the angiogenic response remains controversial. In this study, we investigated whether human fetal lung fibroblasts (MRC-5 cells) exhibit morphological plasticity in a biomimetic extracellular matrix environment. To this end, MRC-5 cells were first cultured on and within [...] Read more.
The role of mesenchymal-to-endothelial transition in the angiogenic response remains controversial. In this study, we investigated whether human fetal lung fibroblasts (MRC-5 cells) exhibit morphological plasticity in a biomimetic extracellular matrix environment. To this end, MRC-5 cells were first cultured on and within Matrigel hydrogel and then studied with tube formation assays, confocal/fluorescence microscopy, invasion assays, and transcriptomic profiling. In addition, quantitative assessment for cord formation and gene expression was conducted via qPCR and RNA sequencing. In this study, MRC-5 cells quickly self-organized into cord-like networks, resembling early stages of vascular patterning, and at higher densities, invaded the hydrogel and formed spheroid-like aggregates. Transcriptomic analysis revealed upregulation of genes related to nervous system development and synaptic signaling in Matrigel-grown MRC-5 cultures. Collectively, these findings suggest that MRC-5 fibroblasts display structural and transcriptional plasticity in 3D Matrigel cultures, forming vascular-like cords that are more likely to resemble early developmental morphologies or neuroectodermal-like transcriptional signatures than definitive endothelial structures. This work underscores the potential of fibroblasts as an alternative cell source for vascular tissue engineering and highlights a strategy to overcome current limitations in autologous endothelial cell availability for regenerative applications. Full article
(This article belongs to the Collection Advances in Epithelial-Mesenchymal Transition (EMT))
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40 pages, 17089 KB  
Review
Advancing Flexible Optoelectronic Synapses and Neurons with MXene-Integrated Polymeric Platforms
by Hongsheng Xu, Xiangyu Zeng and Akeel Qadir
Nanomaterials 2025, 15(19), 1481; https://doi.org/10.3390/nano15191481 - 27 Sep 2025
Viewed by 319
Abstract
Neuromorphic computing, inspired by the human brain’s architecture, offers a transformative approach to overcoming the limitations of traditional von Neumann systems by enabling highly parallel, energy-efficient information processing. Among emerging materials, MXenes—a class of two-dimensional transition metal carbides and nitrides—have garnered significant attention [...] Read more.
Neuromorphic computing, inspired by the human brain’s architecture, offers a transformative approach to overcoming the limitations of traditional von Neumann systems by enabling highly parallel, energy-efficient information processing. Among emerging materials, MXenes—a class of two-dimensional transition metal carbides and nitrides—have garnered significant attention due to their exceptional electrical conductivity, tunable surface chemistry, and mechanical flexibility. This review comprehensively examines recent advancements in MXene-based optoelectronic synapses and neurons, focusing on their structural properties, device architectures, and operational mechanisms. We emphasize synergistic electrical–optical modulation in memristive and transistor-based synaptic devices, enabling improved energy efficiency, multilevel plasticity, and fast response times. In parallel, MXene-enabled optoelectronic neurons demonstrate integrate-and-fire dynamics and spatiotemporal information integration crucial for biologically inspired neural computations. Furthermore, this review explores innovative neuromorphic hardware platforms that leverage multifunctional MXene devices to achieve programmable synaptic–neuronal switching, enhancing computational flexibility and scalability. Despite these promising developments, challenges remain in device stability, reproducibility, and large-scale integration. Addressing these gaps through advanced synthesis, defect engineering, and architectural innovation will be pivotal for realizing practical, low-power optoelectronic neuromorphic systems. This review thus provides a critical roadmap for advancing MXene-based materials and devices toward next-generation intelligent computing and adaptive sensory applications. Full article
(This article belongs to the Section Theory and Simulation of Nanostructures)
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14 pages, 2937 KB  
Article
Organization and Community Usage of a Neuron Type Circuitry Knowledge Base of the Hippocampal Formation
by Kasturi Nadella, Diek W. Wheeler and Giorgio A. Ascoli
Biomedicines 2025, 13(10), 2363; https://doi.org/10.3390/biomedicines13102363 - 26 Sep 2025
Viewed by 200
Abstract
Background/Objectives: Understanding the diverse neuron types within the hippocampal formation is essential for advancing our knowledge of its fundamental roles in learning and memory. Hippocampome.org serves as a comprehensive, evidence-based knowledge repository that integrates morphological, electrophysiological, and molecular features of neurons across [...] Read more.
Background/Objectives: Understanding the diverse neuron types within the hippocampal formation is essential for advancing our knowledge of its fundamental roles in learning and memory. Hippocampome.org serves as a comprehensive, evidence-based knowledge repository that integrates morphological, electrophysiological, and molecular features of neurons across the rodent dentate gyrus, CA3, CA2, CA1, subiculum, and entorhinal cortex. In addition to these core properties, this open access resource includes detailed information on synaptic connectivity, signal propagation, and plasticity, facilitating sophisticated modeling of hippocampal circuits. A distinguishing feature of Hippocampome.org is its emphasis on quantitative, literature-backed data that can help constrain and validate spiking neural network simulations via an interactive web interface. Methods: To assess and enhance its utility to the neuroscience community, we integrated Google Analytics (GA) into the platform to monitor user behavior, identify high-impact content, and evaluate geographic reach. Results: GA data provided valuable page view metrics, revealing usage trends, frequently accessed neuron properties, and the progressive adoption of new functionalities. Conclusions: These insights directly inform iterative development, particularly in the design of a robust Application Programming Interface (API) to support programmatic access. Ultimately, the integration of GA empowers data-driven optimization of this public resource to better serve the global neuroscience community. Full article
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13 pages, 2020 KB  
Article
Substrate Orientation-Dependent Synaptic Plasticity and Visual Memory in Sol–Gel-Derived ZnO Optoelectronic Devices
by Dabin Jeon, Seung Hun Lee, JungBeen Cho, Kyoung-Bo Kim and Sung-Nam Lee
Materials 2025, 18(18), 4377; https://doi.org/10.3390/ma18184377 - 19 Sep 2025
Viewed by 391
Abstract
We report Al/ZnO/Al optoelectronic synaptic devices fabricated on c-plane and m-plane sapphire substrates using a sol–gel process. The devices exhibit essential synaptic behaviors such as excitatory postsynaptic current modulation, paired-pulse facilitation, and long-term learning–forgetting dynamics described by Wickelgren’s power law. Comparative analysis reveals [...] Read more.
We report Al/ZnO/Al optoelectronic synaptic devices fabricated on c-plane and m-plane sapphire substrates using a sol–gel process. The devices exhibit essential synaptic behaviors such as excitatory postsynaptic current modulation, paired-pulse facilitation, and long-term learning–forgetting dynamics described by Wickelgren’s power law. Comparative analysis reveals that substrate orientation strongly influences memory performance: devices on m-plane consistently show higher EPSCs, slower decay rates, and superior retention compared to c-plane counterparts. These characteristics are attributed to crystallographic effects that enhance carrier trapping and persistent photoconductivity. To demonstrate their practical applicability, 3 × 3-pixel arrays of adjacent devices were constructed, where a “T”-shaped optical pattern was successfully encoded, learned, and retained across repeated stimulation cycles. These results highlight the critical role of substrate orientation in tailoring synaptic plasticity and memory retention, offering promising prospects for ZnO-based optoelectronic synaptic arrays in in-sensor neuromorphic computing and artificial visual memory systems. Full article
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9 pages, 2339 KB  
Communication
Controlling the Digital to Analog and Multilevel Switching in Memristors Based on Zr-Doped HfO2 by Interface Engineering
by Cong Han, Haiming Qin, Weijing Shao, Hanbing Fang, Hao Zhang, Xinpeng Wang, Yu Wang, Yi Liu and Yi Tong
Materials 2025, 18(18), 4352; https://doi.org/10.3390/ma18184352 - 17 Sep 2025
Viewed by 371
Abstract
Metal oxides are the most widely used material for the resistive switching layer of memristors. Nevertheless, the majority of oxide-based memristors exhibit binary switching, restricting the emulation of neuronal synaptic behaviors. In this paper, the shift from digital-to-analog switching behavior is achieved by [...] Read more.
Metal oxides are the most widely used material for the resistive switching layer of memristors. Nevertheless, the majority of oxide-based memristors exhibit binary switching, restricting the emulation of neuronal synaptic behaviors. In this paper, the shift from digital-to-analog switching behavior is achieved by inserting an Al2O3 layer atop Zr-doped HfO2. The TiN/Al2O3/HZO/W/Si device exhibits long resistance state retention time and consistency. In addition, by applying a varying voltage, the device exhibits up to 20 continuous resistance states, which is highly significant for high-density storage. Upon the application of a programmable pulse signal, the device’s conductance undergoes continual alteration, reflecting long-term potentiation (LTP) and long-term depression (LTD) synaptic characteristics. The conduction mechanism of the device is studied through physical model fitting and schematic diagrams. Full article
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14 pages, 1848 KB  
Article
X-Ray Irradiation Improved WSe2 Optical–Electrical Synapse for Handwritten Digit Recognition
by Chuanwen Chen, Qi Sun, Yaxian Lu and Ping Chen
Nanomaterials 2025, 15(18), 1408; https://doi.org/10.3390/nano15181408 - 12 Sep 2025
Viewed by 331
Abstract
Two-dimensional (2D) materials are promising candidates for neuromorphic computing owing to their atomically thin structure and tunable optoelectronic properties. However, achieving controllable synaptic behavior via defect engineering remains challenging. In this work, we introduce X-ray irradiation as a facile strategy to modulate defect [...] Read more.
Two-dimensional (2D) materials are promising candidates for neuromorphic computing owing to their atomically thin structure and tunable optoelectronic properties. However, achieving controllable synaptic behavior via defect engineering remains challenging. In this work, we introduce X-ray irradiation as a facile strategy to modulate defect states and enhance synaptic plasticity in WSe2-based optoelectronic synapses. The introduction of selenium vacancies via irradiation significantly improved both electrical and optical responses. Under electrical stimulation, short-term potentiation (STP) exhibited enhanced excitatory postsynaptic current (EPSC) retention exceeding 10%, measured 20 s after the stimulation peak. In addition, the nonlinearity of long-term potentiation (LTP) and long-term depression (LTD) was reduced, and the signal decay time was extended. Under optical stimulation, STP showed more than 4% improvement in EPSC retention at 16 s with similar relaxation enhancement. These effects are attributed to irradiation-induced defect states that facilitate charge carrier trapping and extend signal persistence. Moreover, the reduced nonlinearity in synaptic weight modulation improved the recognition accuracy of handwritten digits in a CrossSim-simulated MNIST task, increasing from 88.5% to 93.75%. This study demonstrates that X-ray irradiation is an effective method for modulating synaptic weights in 2D materials, offering a universal strategy for defect engineering in neuromorphic device applications. Full article
(This article belongs to the Section Nanoelectronics, Nanosensors and Devices)
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14 pages, 2389 KB  
Article
Neural Synaptic Simulation Based on ZnAlSnO Thin-Film Transistors
by Yang Zhao, Chao Wang, Laizhe Ku, Liang Guo, Xuefeng Chu, Fan Yang, Jieyang Wang, Chunlei Zhao, Yaodan Chi and Xiaotian Yang
Micromachines 2025, 16(9), 1025; https://doi.org/10.3390/mi16091025 - 7 Sep 2025
Viewed by 545
Abstract
In the era of artificial intelligence, neuromorphic devices that simulate brain functions have received increasingly widespread attention. In this paper, an artificial neural synapse device based on ZnAlSnO thin-film transistors was fabricated, and its electrical properties were tested: the current-switching ratio was 1.18 [...] Read more.
In the era of artificial intelligence, neuromorphic devices that simulate brain functions have received increasingly widespread attention. In this paper, an artificial neural synapse device based on ZnAlSnO thin-film transistors was fabricated, and its electrical properties were tested: the current-switching ratio was 1.18 × 107, the subthreshold oscillation was 1.48 V/decade, the mobility was 2.51 cm2V−1s−1, and the threshold voltage was −9.40 V. Stimulating artificial synaptic devices with optical signals has the advantages of fast response speed and good anti-interference ability. The basic biological synaptic characteristics of the devices were tested under 365 nm light stimulation, including excitatory postsynaptic current (EPSC), paired-pulse facilitation (PPF), short-term plasticity (STP), and long-term plasticity (LTP). This device shows good synaptic plasticity. In addition, by changing the gate voltage, the excitatory postsynaptic current of the device at different gate voltages was tested, two different logical operations of “AND” and “OR” were achieved, and the influence of different synaptic states on memory was simulated. This work verifies the application potential of the device in the integrated memory and computing architecture, which is of great significance for promoting the high-quality development of neuromorphic computing hardware. Full article
(This article belongs to the Special Issue Advanced Wide Bandgap Semiconductor Materials and Devices)
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21 pages, 679 KB  
Review
The Role of Blood-Based Biomarkers in Transforming Alzheimer’s Disease Research and Clinical Management: A Review
by Vera Pacoova Dal Maschio, Fausto Roveta, Lucrezia Bonino, Silvia Boschi, Innocenzo Rainero and Elisa Rubino
Int. J. Mol. Sci. 2025, 26(17), 8564; https://doi.org/10.3390/ijms26178564 - 3 Sep 2025
Viewed by 1532
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative condition representing the most common cause of dementia and currently affects millions of people worldwide. The clinical presentation includes memory impairment, cognitive decline, and neuropsychiatric symptoms, reflecting pathological hallmarks such as β-amyloid (Aβ) plaques, neurofibrillary tangles, [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative condition representing the most common cause of dementia and currently affects millions of people worldwide. The clinical presentation includes memory impairment, cognitive decline, and neuropsychiatric symptoms, reflecting pathological hallmarks such as β-amyloid (Aβ) plaques, neurofibrillary tangles, synaptic dysfunction, and neuroinflammation. Despite being the gold standard for detecting amyloid and tau pathologies in vivo, cerebrospinal fluid (CSF) biomarkers and positron emission tomography (PET) imaging are not widely used in the clinical setting because of invasiveness, high costs, and restricted accessibility. Recent advances in blood-based biomarkers offer a promising and minimally invasive tool for early detection, diagnosis, and monitoring of AD. Ultra-sensitive analytical platforms, including single-molecule arrays (Simoa) and immunoprecipitation-mass spectrometry, now enable reliable quantification of plasma Aβ isoforms, phosphorylated tau variants (p-Tau181, p-Tau217, p-Tau231), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). In addition, blood biomarkers reflecting oxidative stress, neuroinflammation, synaptic disruption and metabolic dysfunction are under active investigation. This narrative review synthesizes current evidence on blood-based biomarkers in AD, emphasizing their biological relevance, diagnostic accuracy, and clinical applications. Finally, we highlight forthcoming challenges, such as standardization, and future directions, including the use of artificial intelligence in precision medicine. Full article
(This article belongs to the Section Molecular Neurobiology)
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35 pages, 7098 KB  
Review
Recent Advances in Optoelectronic Synaptic Devices for Neuromorphic Computing
by Heeseong Jang, Seohyeon Ju, Seeun Lee, Jaewoo Choi, Ungbin Byun, Kyeongjun Min, Maria Rasheed and Sungjun Kim
Biomimetics 2025, 10(9), 584; https://doi.org/10.3390/biomimetics10090584 - 3 Sep 2025
Viewed by 1283
Abstract
We explore recent advancements in optoelectronic synaptic devices across four key aspects: mechanisms, materials, synaptic properties, and applications. First, we discuss fundamental working principles, including oxygen vacancy ionization, defect trapping, and heterojunction-based charge modulation, which contribute to synaptic plasticity. Next, we examine the [...] Read more.
We explore recent advancements in optoelectronic synaptic devices across four key aspects: mechanisms, materials, synaptic properties, and applications. First, we discuss fundamental working principles, including oxygen vacancy ionization, defect trapping, and heterojunction-based charge modulation, which contribute to synaptic plasticity. Next, we examine the role of 0D, 1D, and 2D materials in optimizing device performance, focusing on their unique electronic, optical, and mechanical properties. We then analyze synaptic properties such as excitatory post-synaptic current (EPSC), visual adaptation, transition from short-term to long-term plasticity (STP to LTP), nociceptor-inspired responses, and associative learning mechanisms. Finally, we highlight real-world applications, including artificial vision systems, reservoir computing for temporal data processing, adaptive neuromorphic computing for exoplanet detection, and colored image recognition. By consolidating recent developments, this paper provides insights into the potential of optoelectronic synaptic devices for next-generation computing architectures, bridging the gap between optics and neuromorphic engineering. Full article
(This article belongs to the Special Issue Bio-Inspired Machine Learning and Evolutionary Computing)
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19 pages, 1366 KB  
Review
Ketamine’s Role in Neuroinflammation and Neuroprotection Across Neurological and Psychiatric Disorders: A Narrative Review
by Gustavo N. Silva, Virna G. A. Brandão, Kenneth Blum, Kai-Uwe Lewandrowski and Rossano K. A. Fiorelli
Pharmaceuticals 2025, 18(9), 1298; https://doi.org/10.3390/ph18091298 - 29 Aug 2025
Viewed by 1223
Abstract
Ketamine, a widely used anesthetic with emerging evidence suggesting neuroprotective and anti-inflammatory properties across various neurological disorders, is recognized for its NMDA receptor antagonism. It has been postulated to play a role in neuroprotection, due to its anti-inflammatory properties, and decrease microglial activation, [...] Read more.
Ketamine, a widely used anesthetic with emerging evidence suggesting neuroprotective and anti-inflammatory properties across various neurological disorders, is recognized for its NMDA receptor antagonism. It has been postulated to play a role in neuroprotection, due to its anti-inflammatory properties, and decrease microglial activation, as well as cytokines TNF and IL-6. Despite its established role, the extent of ketamine’s effects on neuroinflammation and neuroprotection remains to be fully elucidated. Here, we conducted a narrative review synthesizing current knowledge on ketamine’s operating mechanisms, including its modulation of synaptic plasticity, excitotoxicity, and cytokine release, alongside its therapeutic applications in traumatic brain injury, neurodegenerative diseases, psychiatric disorders, and pain management. For this narrative review, we searched the Medline, Embase, Scopus, Web of Science, and PubMed databases. Our findings indicate that ketamine reduces excitotoxicity and inflammation, which may contribute to neuroprotection in acute neurological injuries. These insights underscore ketamine’s potential as an adjunctive neuroprotective agent, warranting further clinical investigation to optimize its therapeutic utility across neurological and psychiatric contexts. Full article
(This article belongs to the Special Issue Pharmacological Insight into NMDA Receptor Antagonists)
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26 pages, 1102 KB  
Review
HDACs in the Brain: From Chromatin Remodeling to Neurodegenerative Disease
by Luan Pereira Diniz, Pedro de Sena Murteira Pinheiro, Lucas S. Franco and Flávia Carvalho Alcantara Gomes
Cells 2025, 14(17), 1338; https://doi.org/10.3390/cells14171338 - 29 Aug 2025
Viewed by 1159
Abstract
Histone deacetylases (HDACs) are key epigenetic regulators that influence chromatin remodeling, gene expression, and cellular plasticity in the central nervous system (CNS). This review provides a comprehensive overview of the classification and functional diversity of HDACs, with particular emphasis on their roles in [...] Read more.
Histone deacetylases (HDACs) are key epigenetic regulators that influence chromatin remodeling, gene expression, and cellular plasticity in the central nervous system (CNS). This review provides a comprehensive overview of the classification and functional diversity of HDACs, with particular emphasis on their roles in neural progenitor cells, mature neurons, and glial populations. In neural stem and progenitor cells, HDACs modulate neurogenesis, fate specification, and lineage commitment. In differentiated neurons, HDACs govern synaptic plasticity, memory formation, and survival. In glial cells, including astrocytes and microglia, HDACs orchestrate inflammatory responses, redox balance, and metabolic adaptations. We further examine the dysregulation of HDAC expression and activity in major neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Evidence from human post-mortem brain studies reveals region- and isoform-specific alterations in HDAC expression, which are closely associated with cognitive decline, mitochondrial dysfunction, and neuroinflammation. Preclinical studies support the use of HDAC inhibitors (HDACi) as neuroprotective agents, capable of restoring acetylation homeostasis, reducing neuroinflammation, and improving neuronal function. Given the relevance of HDACi, we summarize current clinical studies assessing the safety of these compounds in the context of tumor biology, as well as their potential future applications in neurodegenerative diseases. Together, this review underscores the dual significance of HDACs as biomarkers and therapeutic targets in the context of CNS disorders. Full article
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18 pages, 10575 KB  
Article
Generation of Active Neurons from Mouse Embryonic Stem Cells Using Retinoic Acid and Purmorphamine
by Ruby Vajaria, DeAsia Davis, Francesco Tamagnini, Duncan G. G. McMillan, Nandini Vasudevan and Evangelos Delivopoulos
Int. J. Mol. Sci. 2025, 26(17), 8372; https://doi.org/10.3390/ijms26178372 - 28 Aug 2025
Viewed by 536
Abstract
Multiple differentiation protocols have emerged in recent years, producing neurons with diverse morphologies, gene and protein expression profiles, and functionality. Many of these differentiation techniques require months of culture and the use of expensive growth factors. Most importantly, the derived neurons usually do [...] Read more.
Multiple differentiation protocols have emerged in recent years, producing neurons with diverse morphologies, gene and protein expression profiles, and functionality. Many of these differentiation techniques require months of culture and the use of expensive growth factors. Most importantly, the derived neurons usually do not exhibit any electrical activity. This limits the value of the protocol as a tool for engineering and investigating neural networks. Here, we describe an efficacious method for differentiating mouse embryonic stem cells into functional neurons. CGR8 cells were neurally induced via the simultaneous application of retinoic acid and purmorphamine. The derived cells expressed neuronal (TUJ1 and NeuN) and synaptic (GAD2, PSD-95, Synaptophysin, and VGLUT1) markers. During whole-cell recordings, neurons exhibited inward and outward currents, likely caused by fast-inactivating voltage-gated potassium channels. Upon current injection, miniature action potentials were also recorded. The efficient generation of diverse subtypes of functional neurons can be a useful tool in fundamental investigations of neural network activity and translational studies. Full article
(This article belongs to the Special Issue Neural Stem Cells: Latest Applications and Future Perspectives)
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11 pages, 1236 KB  
Article
Structure-Based Engineering of a PTPsigma Ectodomain for Enhanced Solubility and Productivity
by Sung Ho Park, Woochan Lim, Jian Kang, Sumin Jo, Hye Hyeon Jang, Heejin Yang, Suk Hyun Yoo, Myeongbin Kim and Seong Eon Ryu
Int. J. Mol. Sci. 2025, 26(17), 8345; https://doi.org/10.3390/ijms26178345 - 28 Aug 2025
Viewed by 400
Abstract
Protein tyrosine phosphatase receptor sigma (PTPRS) regulates cellular signals involved in hematopoietic stem cell development, synaptic plasticity, and synovium differentiation. The soluble extracellular Ig-like domains of PTPRS have therapeutic potential by binding to a ligand, inhibiting the ligand-binding of endogenous PTPRS. However, the [...] Read more.
Protein tyrosine phosphatase receptor sigma (PTPRS) regulates cellular signals involved in hematopoietic stem cell development, synaptic plasticity, and synovium differentiation. The soluble extracellular Ig-like domains of PTPRS have therapeutic potential by binding to a ligand, inhibiting the ligand-binding of endogenous PTPRS. However, the wild-type Ig-like domains have poor solubility, which limits their therapeutic use. In this study, we identified solvent-exposed hydrophobic residues on the surface of PTPRS and mutated the residues to hydrophilic residues for solubility-enhancing engineering. The mutagenesis screening increased its solubility up to five-fold. In addition, the expression yields were also increased by up to 14-fold. The biochemical and functional analysis of the engineered PTPRS showed that the mutant protein had comparable properties to the wild type. Thus, the engineered PTPRS has potential for therapeutic applications where modulation of PTPRS is critical. Full article
(This article belongs to the Special Issue Biomolecular Structure, Function and Interactions: 2nd Edition)
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