Treatment Of Neurological Disorders Research Articles

The anti-neuroinflammatory effects of cepharanthine in uric acid-induced neuroinflammation.

Cepharanthine (CEP) is an alkaloid extracted from Stephania cephalantha Hayata, a traditional Chinese medicine (TCM) renowned for its heatclearing and dehumidifying properties. For centuries, Stephania cephalantha Hayata has been employed in the treatment of a wide range of diseases, including pain, edema, inflammation, and fever. Our research aims to investigate the role and mechanism of Cepharanthine in ameliorating uric acid (UA) induced neuroinflammatory responses. The Connectivity Map (CMap) was utilized to identify the therapeutic drug Cepharanthine, based on the proteomic disturbances associated with uric acid (UA). Limited proteolysis small molecule mapping (LiP-SMap) and thermal proteome profiling (TPP) technologies were used to identify the direct target proteins for UA and Cepharanthine. Additionally, we used the induced-fit docking algorithm integrated within the Schrodinger suite to explore the interactions between Cepharanthine and uric acid targets. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology was employed to determine the concentration of Cepharanthine in the mice cerebral cortex. The pro-inflammatory cytokine genes were also quantified by qPCR in U251cells and in hyperuricemic mice. The findings indicated that uric acid increased the transcription of pro-inflammatory cytokines and the expression levels of proteins linked to inflammation in U251cells. PPP2R1A was identified as a potential candidate for direct interaction with uric acid, potentially initiating inflammation. Based on the CMap prediction, Cepharanthine was identified as a candidate drug for interaction with PPP2R1A. TPP analysis indicated that Cepharanthine could reduce the thermal stability of PPP2R1A. Molecular docking confirmed that Cepharanthine could directly bind to PPP2R1A. Furthermore, the detection of Cepharanthine in the cerebral cortex suggested its ability to cross the blood-brain barrier. Proteomic analysis of Cepharanthine-treated mice revealed significant enrichments of differentially expressed proteins (DEPs) in inflammation-related pathways and biological processes. Additionally, Cepharanthine was effective in decreasing the expression of pro-inflammatory cytokine genes induced by uric acid in U251cells and in hyperuricemic mice. Cepharanthine could effectively alleviate hyperuricemia-induced neuroinflammation via binding to PPP2R1A. This study offers a novel approach for prevention and treatment of neurological diseases caused by hyperuricemia.

Current Advances and Challenges in Gene Therapies for Neurologic Disorders: A Review for the Clinician.

Over 300 million people globally are affected by rare diseases, many of which present predominantly with neurologic symptoms. Rare neurologic disorders pose significant diagnostic and therapeutic challenges including delayed diagnoses, limited treatment options, and a shortage of specialists. However, advancements in diagnostics, particularly next-generation sequencing and expansion of newborn screening, have significantly shortened the time to diagnosis for many of these disorders. Concurrently, the past decade has witnessed exponential development of new treatments for rare neurologic diseases, with several approved gene therapies and more trials under way. A range of targeted therapies now offers hope for not only symptomatic management but also for disease modification. As treatments transition from clinical trials to clinical practice, the responsibility of identifying and monitoring patients may increasingly fall on the general neurologists. This evolving therapeutic landscape highlights the urgent need to enhance our understanding of this new class of medications and the details on clinical eligibility and monitoring of patients with diseases that have approved gene therapies. This article provides a comprehensive overview of gene-targeted therapies currently available for neurologic disorders, with a focus on their mechanisms, challenges, and post-treatment considerations.

The roles and therapeutic potential of exosomal non-coding RNAs in microglia-mediated intercellular communication.

Exosomes, which are small extracellular vesicles (sEVs), serve as versatile regulators of intercellular communication in the progression of various diseases, including neurological disorders. Among the diverse array of cargo they carry, non-coding RNAs (ncRNAs) play key regulatory roles in various pathophysiological processes. Exosomal ncRNAs derived from distinct cells modulate their reciprocal crosstalk locally or remotely, thereby mediating neurological diseases. Nevertheless, the emerging role of exosomal ncRNAsin microglia-mediated phenotypes remains largely unexplored. This review aims to summarise the biological functions of exosomal ncRNAs and the molecular mechanisms that underlie their impact on microglia-mediated intercellular communication, modulating neuroinflammation and synaptic functions within the landscape of neurological disorders. Furthermore, this review comprehensively described the potential applications of exosomal ncRNAs as diagnostic and prognostic biomarkers, as well as innovative therapeutic targets for the treatment of neurological diseases.

Vaccine Based Approaches for the Prevention and Treatment of Neurological Disease

Vaccine Based Approaches for the Prevention and Treatment of Neurological Disease

Dental Pulp Stem Cells Attenuate Early Brain Injury After Subarachnoid Hemorrhage via miR-26a-5p/PTEN/AKT Pathway.

Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke with high morbidity, mortality and disability, and early brain injury (EBI) after SAH is crucial for prognosis. Recently, stem cell therapy has garnered significant attention in the treatment of neurological diseases. Compared to other stem cells, dental pulp stem cells (DPSCs) possess several advantages, including abundant sources, absence of ethical concerns, non-invasive procurement, non-tumorigenic history and neuroprotective potential. Therefore, we aim to investigate whether DPSCs can improve EBI after SAH, and explore the mechanisms. In our study, we utilized the endovascular perforation method to establish a SAH mouse model and investigated whether DPSCs administered via tail vein injection could improve EBI after SAH. Furthermore, we used hemin-stimulated HT22 cells to simulate neuronal cell injury induced by SAH and employed a co-culture approach to examine the effects of DPSCs on these cells. To gain insights into the potential mechanisms underlying the improvement of SAH-induced EBI by DPSCs, we conducted bioinformatics analysis. Finally, we further validated our findings through experiments. In vivo experiments, we found that DPSCs administration improved neurological dysfunction, reduced brain edema, and prevented neuronal apoptosis in SAH mice. Additionally, we observed a decrease in the expression level of miR-26a-5p in the cortical tissues of SAH mice, which was significantly increased following intravenous injection of DPSCs. Through bioinformatic analysis and luciferase reporter assay, we confirmed the target relationship between miR-26a-5p and PTEN. Moreover, we demonstrated that DPSCs exerted neuroprotective effects by modulating the miR-26a-5p/PTEN/AKT pathway. Our study demonstrates that DPSCs can improve EBI after SAH through the miR-26a-5p/PTEN/AKT pathway, laying a foundation for the application of DPSCs in SAH treatment. These findings provide a theoretical basis for further investigating the therapeutic mechanisms of DPSCs and developing novel treatment strategies in SAH.

Advances in clinical translation of stem cell-based therapy in neurological diseases.

Stem cell-based therapies have raised considerable interest to develop regenerative treatment for neurological disorders with high disability. In this review, we focus on recent preclinical and clinical evidence of stem cell therapy in the treatment of degenerative neurological diseases and discuss different cell types, delivery routes and biodistribution of stem cell therapy. In addition, recent advances of mechanistic insights of stem cell therapy, including functional replacement by exogenous cells, immunomodulation and paracrine effects of stem cell therapies are also demonstrated. Finally, we also highlight the adjunction approaches that has been implemented to augment their reparative function, survival and migration to target specific tissue, including stem cell preconditioning, genetical engineering, co-transplantation and combined therapy.

Increasing brain half-life of antibodies by additional binding to myelin oligodendrocyte glycoprotein, a CNS specific protein.

Therapeutic antibodies for the treatment of neurological disease show great potential, but their applications are rather limited due to limited brain exposure. The most well-studied approach to enhance brain influx of protein therapeutics, is receptor-mediated transcytosis (RMT) by targeting nutrient receptors to shuttle protein therapeutics over the blood-brain barrier (BBB) along with their endogenous cargos. While higher brain exposure is achieved with RMT, the timeframe is short due to rather fast brain clearance. Therefore, we aim to increase the brain half-life of antibodies by binding to myelin oligodendrocyte glycoprotein (MOG), a CNS specific protein. Alpaca immunization with mouse/human MOG, and subsequent phage selections and screenings for MOG binding single variable domain antibodies (VHHs) were performed to find mouse/human cross-reactive VHHs. Their ability to increase the brain half-life of antibodies was evaluated in healthy wild-type mice by coupling two different MOG VHHs (low/high affinity) in a mono- and bivalent format to a β-secretase 1 (BACE1) inhibiting antibody or a control (anti-SARS-CoV-2) antibody, fused to an anti-transferrin receptor (TfR) VHH for active transport over the BBB. Brain pharmacokinetics and pharmacodynamics, CNS and peripheral biodistribution, and brain toxicity were evaluated after intravenous administration to balb/c mice. Additional binding to MOG increases the Cmax and brain half-life of antibodies that are actively shuttled over the BBB. Anti-SARS-CoV-2 antibodies coupled with an anti-TfR VHH and two low affinity anti-MOG VHHs could be detected in brain 49days after a single intravenous injection, which is a major improvement compared to an anti-SARS-CoV-2 antibody fused to an anti-TfR VHH which cannot be detected in brain anymore one week post treatment. Additional MOG binding of antibodies does not affect peripheral biodistribution but alters brain distribution to white matter localization and less neuronal internalization. We have discovered mouse/human/cynomolgus cross-reactive anti-MOG VHHs which have the ability to drastically increase brain exposure of antibodies. Combining MOG and TfR binding leads to distinct PK, biodistribution, and brain exposure, differentiating it from the highly investigated TfR-shuttling. It is the first time such long brain antibody exposure has been demonstrated after one single dose. This new approach of adding a binding moiety for brain specific targets to RMT shuttling antibodies is a huge advancement for the field and paves the way for further research into brain half-life extension.

Transformers for Neuroimage Segmentation: Scoping Review.

Neuroimaging segmentation is increasingly important for diagnosing and planning treatments for neurological diseases. Manual segmentation is time-consuming, apart from being prone to human error and variability. Transformers are a promising deep learning approach for automated medical image segmentation. This scoping review will synthesize current literature and assess the use of various transformer models for neuroimaging segmentation. A systematic search in major databases, including Scopus, IEEE Xplore, PubMed, and ACM Digital Library, was carried out for studies applying transformers to neuroimaging segmentation problems from 2019 through 2023. The inclusion criteria allow only for peer-reviewed journal papers and conference papers focused on transformer-based segmentation of human brain imaging data. Excluded are the studies dealing with nonneuroimaging data or raw brain signals and electroencephalogram data. Data extraction was performed to identify key study details, including image modalities, datasets, neurological conditions, transformer models, and evaluation metrics. Results were synthesized using a narrative approach. Of the 1246 publications identified, 67 (5.38%) met the inclusion criteria. Half of all included studies were published in 2022, and more than two-thirds used transformers for segmenting brain tumors. The most common imaging modality was magnetic resonance imaging (n=59, 88.06%), while the most frequently used dataset was brain tumor segmentation dataset (n=39, 58.21%). 3D transformer models (n=42, 62.69%) were more prevalent than their 2D counterparts. The most developed were those of hybrid convolutional neural network-transformer architectures (n=57, 85.07%), where the vision transformer is the most frequently used type of transformer (n=37, 55.22%). The most frequent evaluation metric was the Dice score (n=63, 94.03%). Studies generally reported increased segmentation accuracy and the ability to model both local and global features in brain images. This review represents the recent increase in the adoption of transformers for neuroimaging segmentation, particularly for brain tumor detection. Currently, hybrid convolutional neural network-transformer architectures achieve state-of-the-art performances on benchmark datasets over standalone models. Nevertheless, their applicability remains highly limited by high computational costs and potential overfitting on small datasets. The heavy reliance of the field on the brain tumor segmentation dataset hints at the use of a more diverse set of datasets to validate the performances of models on a variety of neurological diseases. Further research is needed to define the optimal transformer architectures and training methods for clinical applications. Continuing development may make transformers the state-of-the-art for fast, accurate, and reliable brain magnetic resonance imaging segmentation, which could lead to improved clinical tools for diagnosing and evaluating neurological disorders.

Copper-Induced Neurodegenerative Disorders and Therapeutic Potential of Curcumin-Loaded Nanoemulsion

Copper accumulation in neurons induces oxidative stress, disrupts mitochondrial activity, and accelerates neuronal death, which is central to the pathophysiology of neurodegenerative diseases like Wilson disease. Standard treatments for copper toxicity, such as D-penicillamine, trientine, and chloroquine, are frequently associated with severe side effects, creating a need for safer therapeutic alternatives. To address this, we developed a curcumin-loaded nanoemulsion (CUR-NE) using the spontaneous emulsification technique, aimed at enhancing the bioavailability and therapeutic efficacy of curcumin. The optimized nanoemulsion displayed a particle size of 76.42 nm, a zeta potential of −20.4 mV, and a high encapsulation efficiency of 93.69%, with a stable and uniform structure. The in vitro tests on SH-SY5Y neuroblastoma cells demonstrated that CUR-NE effectively protected against copper-induced toxicity, promoting significant cellular uptake. Pharmacokinetic studies revealed that CUR-NE exhibited a longer half-life and extended circulation time compared to free curcumin. Additionally, pharmacodynamic evaluations, including biochemical assays and histopathological analysis, confirmed that CUR-NE provided superior neuroprotection in copper overload conditions. These results emphasize the ability of CUR-NE to augment the therapeutic effects of curcumin, presenting a novel approach for managing copper-induced neurodegeneration. The study highlights the effectiveness of nanoemulsion-based delivery platforms in improving chelation treatments for neurological diseases.

Pre-clinical acute oral toxicity and subacute neurotoxicity risk assessments on sprague dawley rats treated with single dose or repeated doses of flavonoid-enriched fraction extracted from Oroxylum indicum leaves

Oroxylum indicum possesses promising flavonoid secondary metabolites. However, translation of these compounds into clinical practice for neurological disease treatment is halted as the toxicity and safety profile of the plant extracts are yet to be determined. This study was conducted to assess the acute oral toxicity and subacute neurotoxicity that could be imposed by the flavonoid-enriched fraction (FEF) extracted from O. indicum leaves, by strictly following the procedures set in Organization for Economic Co-operation and Development (OECD) Guidelines No.420 and 424. It was found that at the highest dosage (2000 mg/kg b.wt), no death or toxicity-related behavioral changes were observed. No significant alteration in hematological and serum biochemical parameters beyond the standard laboratory range was observed. Detailed histopathological examination, as verified by clinical pathologist, revealed absence of detectable inflammation, changes in any macroscopic and microscopic tissue abnormalities in all vital organ of the treated rats. Moreover, neurological functional test of rats treated with repeated doses of FEF for 28 d also showed absence of neurological abnormality, suggesting negative long term side effects of this fraction on the animal. In conclusion, this study presented valuable pre-clinical safety validation of a high-quality herbal medicinal product, setting the foundation for its future application in clinical setting.

Development of an Automated Diagnostic System using Genetic Algorithms in Electroneurodiagnostic Data

This project aims to develop an automated diagnostic system that leverages genetic algorithms (GAs) for analyzing electroneurodiagnostic (END) data, including electroencephalograms (EEG) and electromyograms (EMG). The growing complexity of END data poses significant challenges for accurate diagnosis and timely intervention in neurological disorders. By utilizing genetic algorithms, we aim to enhance the feature selection process, optimizing the identification of relevant patterns associated with various neurological conditions. The system will undergo rigorous training using a diverse dataset, allowing it to recognize and classify abnormalities effectively. Initial results indicate that GAs can significantly improve diagnostic accuracy compared to traditional methods, reducing the likelihood of misdiagnosis and facilitating early intervention. The project also aims to establish a user-friendly interface for clinicians, enabling them to interpret results intuitively. This innovative approach enhances diagnostic capabilities and contributes to neuroinformatics, promoting the integration of artificial intelligence in clinical practice.

A bibliometric analysis of studies on artificial intelligence in neuroscience

The incorporation of artificial intelligence (AI) into neuroscience has the potential to significantly enhance our comprehension of brain function and facilitate more effective diagnosis and treatment of neurological disorders. Artificial intelligence (AI) techniques, particularly deep learning and machine learning, offer transformative solutions by improving the analysis of complex neural data, facilitating early diagnosis, and enabling personalized treatment approaches. A bibliometric analysis is a method that employs quantitative techniques for the examination of scientific literature, with the objective of identifying trends in research, evaluating the impact of influential studies, and mapping the networks of collaboration. In light of the accelerated growth and interdisciplinary scope of AI applications in neuroscience, a bibliometric analysis is vital for mapping the landscape, identifying pivotal contributions, and underscoring emerging areas of interest. This study aims to address this need by examining 1,208 studies published between 1983 and 2024 from the Web of Science database. The analysis reveals a notable surge in publications since the mid-2010s, with substantial advancements in neurological imaging, brain-computer interfaces (BCI), and the diagnosis and treatment of neurological diseases. The analysis underscores the pioneering role of countries such as the United States, China, and the United Kingdom in this field and highlights the prevalence of international collaboration. This study offers a comprehensive overview of the current state and future directions of AI applications in neuroscience, as well as an examination of the transformative potential of AI in advancing neurological research and healthcare. It is recommended that future research address the ethical issues, data privacy concerns, and interpretability of AI models in order to fully capitalize on the benefits of AI in neuroscience.

Stimuli-Responsive Nano Drug Delivery Systems for the Treatment of Neurological Diseases.

Nanomaterials with unparalleled physical and chemical attributes have become a cornerstone in the field of nanomedicine delivery. These materials can be engineered into various functionalized nanocarriers, which have become the focus of research. Stimulus-responsive nanodrug delivery systems (SRDDS) stand out as a sophisticated class of nanocarriers that can release drugs in response to environmental cues. Due to the complex pathogenesis and the multifaceted pathological environment of the nervous system, developing accurate and effective drug therapy with low side-effects is a formidable task. In recent years, SRDDS have been widely used in the treatment of neurological diseases. By customizing SRDDS to align with the specific microenvironment of the nervous system tissues or external stimulation, the efficacy of drug delivery can be enhanced. This review provides an in-depth look at the characteristics of the microenvironment of neurological diseases and highlights case studies of SRDDS tailored to treat these disorders based on theunique stimulation criteria of nervous system tissues or external triggers. Additionally, this review provides a comprehensive overview of the progress and future prospects of SRDDS technology in the treatment of neurological diseases, providing valuable guidance for its transition from fundamental research to clinical application.

Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease.

The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics. These approaches each have their advantages and disadvantages. CSF delivery and intracranial delivery are direct but invasive techniques that have not yet shown efficacy in clinical trials, although development of novel delivery devices might improve these approaches. Ultrasound-based disruption has shown some efficacy in clinical trials, but it can require invasive procedures. Approaches using membrane transporters and receptor-mediated transcytosis are less invasive than are other techniques, but they can have off-target effects. Nanotherapeutics have shown promise, but these strategies are in early stages of development. Advancements in drug delivery across the blood-brain barrier will require appropriately designed and powered clinical studies, with a focus on the timing of treatment, demographic and genetic considerations, head-to-head comparison with other treatment strategies (rather than a placebo), and relevant primary and secondary outcome measures.

Novel strategies targeting mitochondria-lysosome contact sites for the treatment of neurological diseases.

Mitochondria and lysosomes are critical for neuronal homeostasis, as highlighted by their dysfunction in various neurological diseases. Recent studies have identified dynamic membrane contact sites between mitochondria and lysosomes, independent of mitophagy and the lysosomal degradation of mitochondrial-derived vesicles (MDVs), allowing bidirectional crosstalk between these cell compartments, the dynamic regulation of organelle networks, and substance exchanges. Emerging evidence suggests that abnormalities in mitochondria-lysosome contact sites (MLCSs) contribute to neurological diseases, including Parkinson's disease, Charcot-Marie-Tooth (CMT) disease, lysosomal storage diseases, and epilepsy. This article reviews recent research advances regarding the tethering processes, regulation, and function of MLCSs and their role in neurological diseases.

Innovative applications of nanotechnology in neuroscience and brain-computer interfaces

The innovative application of nanotechnology in neuroscience and brain-computer interfaces is running a revolutionary revolution. By precisely controlling ministerial size, shape and surface properties, scientists have designed highly compatible nanomaterials with neural cells and show great potential in accurately recording and stimulating neural signals and the regeneration and repair of neural tissue. These innovative applications not only improve our cognition and understanding of the nervous system but also offer new strategies and tools for the treatment of neurological diseases. The application of nanotechnology in neuroscience and brain-computer interfaces also faces challenges in biocompatibility, safety, long-term effects, and cost. In the future, with the continuous progress of technology and the deepening of interdisciplinary research, we have reason to believe that nanotechnology will play a more important role in the interface of neuroscience and brain-computer, and make a greater contribution to the cause of human health. This paper reviews the latest research achievements and technological progress in this field, prospects for its future trends and identifies the challenges and research directions to follow.

Advances in physiological and clinical relevance of hiPSC-derived brain models for precision medicine pipelines.

Precision, or personalized, medicine aims to stratify patients based on variable pathogenic signatures to optimize the effectiveness of disease prevention and treatment. This approach is favorable in the context of brain disorders, which are often heterogeneous in their pathophysiological features, patterns of disease progression and treatment response, resulting in limited therapeutic standard-of-care. Here we highlight the transformative role that human induced pluripotent stem cell (hiPSC)-derived neural models are poised to play in advancing precision medicine for brain disorders, particularly emerging innovations that improve the relevance of hiPSC models to human physiology. hiPSCs derived from accessible patient somatic cells can produce various neural cell types and tissues; current efforts to increase the complexity of these models, incorporating region-specific neural tissues and non-neural cell types of the brain microenvironment, are providing increasingly relevant insights into human-specific neurobiology. Continued advances in tissue engineering combined with innovations in genomics, high-throughput screening and imaging strengthen the physiological relevance of hiPSC models and thus their ability to uncover disease mechanisms, therapeutic vulnerabilities, and tissue and fluid-based biomarkers that will have real impact on neurological disease treatment. True physiological understanding, however, necessitates integration of hiPSC-neural models with patient biophysical data, including quantitative neuroimaging representations. We discuss recent innovations in cellular neuroscience that can provide these direct connections through generative AI modeling. Our focus is to highlight the great potential of synergy between these emerging innovations to pave the way for personalized medicine becoming a viable option for patients suffering from neuropathologies, particularly rare epileptic and neurodegenerative disorders.

Alkaloid-rich fraction from Luffa cylindrica Linn fruit enhances memory and mitigates oxidative stress in hippocampus of ozone-exposed sprague Dawley rat via LCMS and network pharmacology approach.

Luffa cylindrica (L.), is a medicinal plant aimed to investigate the efficacy of the alkaloid-rich fraction (ARF) extracted from L. cylindrica. The study employed behavioural analysis of rat using Morris water maze (MWM), biochemical analysis of apoptotic proteins, Immunohistochemistry of caspase 3 protein and network pharmacology approach. The ozone-induced group exhibited complex behavioral changes. Western blot analysis revealed altered expression of SOD2, Caspase 3, and Cytochrome C which play integral roles in oxidative stress, apoptosis, and mitochondrial function. Histopathological analysis of the hippocampus further supported the neuroprotective potential of L. cylindrica, demonstrating a reduction in neuropathological lesions and improved memory processes. Network Pharmacology showed the implication of GSK3β in neuronal damage. ARF showed promise in preventing further neuronal damage. In summary, this comprehensive study sheds light on its potential in neuroprotective applications by in vivo behavioral and molecular analyses. It provides a holistic understanding of the medicinal properties of ARF, encouraging further exploration for potential therapeutic interventions in neurological diseases.

Growth and differentiation factor 15: An emerging therapeutic target for brain diseases

Growth and differentiation factor 15 (GDF15), a member of the transforming growth factor-βsuperfamily, is considered a stress response factor and has garnered increasing attention in recent years due to its roles in neurological diseases. Although many studies have suggested that GDF15 expression is elevated in patients with neurodegenerative diseases (NDDs), glioma, and ischemic stroke, the effects of increased GDF15 expression and the potential underlying mechanisms remain unclear. Notably, many experimental studies have shown the multidimensional beneficial effects of GDF15 on NDDs, and GDF15 overexpression is able to rescue NDD-associated pathological changes and phenotypes. In glioma, GDF15 exerts opposite effects, it is both protumorigenic and antitumorigenic. The causes of these conflicting findings are not comprehensively clear, but inhibiting GDF15 is helpful for suppressing tumor progression. GDF15 is also regarded as a biomarker of poor clinical outcomes in ischemic stroke patients, and targeting GDF15 may help prevent this disease. Thus, we systematically reviewed the synthesis, transcriptional regulation, and biological functions of GDF15 and its related signaling pathways within the brain. Furthermore, we explored the potential of GDF15 as a therapeutic target and assessed its clinical applicability in interventions for brain diseases. By integrating the latest research findings, this study provides new insights into the future treatment of neurological diseases.

Understanding the intricacies of cellular mechanisms in remyelination: The role of circadian rhythm.

The term "circadian rhythm" refers to the 24-h oscillations found in various physiological processes in organisms, responsible for maintaining bodily homeostasis. Many neurological diseases mainly involve the process of demyelination, and remyelination is crucial for the treatment of neurological diseases. Current research mainly focuses on the key role of circadian clocks in the pathophysiological mechanisms of multiple sclerosis. Various studies have shown that the circadian rhythm regulates various cellular molecular mechanisms and signaling pathways involved in remyelination. The process of remyelination is primarily mediated by oligodendrocyte precursor cells (OPCs), oligodendrocytes, microglia, and astrocytes. OPCs are activated, proliferate, migrate, and ultimately differentiate into oligodendrocytes after demyelination, involving many key signaling pathway and regulatory factors. Activated microglia secretes important cytokines and chemokines, promoting OPC proliferation and differentiation, and phagocytoses myelin debris that inhibits remyelination. Astrocytes play a crucial role in supporting remyelination by secreting signals that promote remyelination or facilitate the phagocytosis of myelin debris by microglia. Additionally, cell-to-cell communication via gap junctions allows for intimate contact between astrocytes and oligodendrocytes, providing metabolic support for oligodendrocytes. Therefore, gaining a deeper understanding of the mechanisms and molecular pathways of the circadian rhythm at various stages of remyelination can help elucidate the fundamental characteristics of remyelination and provide insights into treating demyelinating disorders.