Disease Of Central Nervous System Research Articles

A No-Brainer! The Therapeutic Potential of TRIM Proteins in Viral and Central Nervous System Diseases.

Tripartite motif (TRIM) proteins comprise an important class of E3 ubiquitin ligases that regulate numerous biological processes including protein expression, cellular signaling pathways, and innate immunity. This ubiquitous participation in fundamental aspects of biology has made TRIM proteins a focus of study in many fields and has illuminated the negative impact they exert when functioning improperly. Disruption of TRIM function has been linked to the success of various pathogens and separately to the occurrence and development of several neurodegenerative diseases, making TRIM proteins an appealing candidate to study for novel therapeutic approaches. Here, we review the current findings on TRIM proteins that demonstrate their analogous properties in the distinct fields of viral infection and central nervous system (CNS) disorders. We also examine recent advancements in drug development and targeted protein degradation as potential strategies for TRIM-mediated therapeutic treatments and discuss the implications these technologies have on future research directions.

Oligodendrocyte-derived IL-33 regulates self-reactive CD8+ T cells in CNS autoimmunity.

In chronic inflammatory disorders of the central nervous system (CNS), tissue-resident self-reactive T cells perpetuate disease. The specific tissue factors governing the persistence and continuous differentiation of these cells remain undefined but could represent attractive therapeutic targets. In a model of chronic CNS autoimmunity, we find that oligodendrocyte-derived IL-33, an alarmin, is key for locally regulating the pathogenicity of self-reactive CD8+ T cells. The selective ablation of IL-33 from neo-self-antigen-expressing oligodendrocytes mitigates CNS disease. In this context, fewer self-reactive CD8+ T cells persist in the inflamed CNS, and the remaining cells are impaired in generating TCF-1low effector cells. Importantly, interventional IL-33 blockade by locally administered somatic gene therapy reduces T cell infiltrates and improves the disease course. Our study identifies oligodendrocyte-derived IL-33 as a druggable tissue factor regulating the differentiation and survival of self-reactive CD8+ T cells in the inflamed CNS. This finding introduces tissue factors as a novel category of immune targets for treating chronic CNS autoimmune diseases.

The Impact of Comorbidities on the Treatment Outcome in Patients With Severe Covid-19-Associated Pneumonia

BACKGROUND. A significant role in the course and outcome of COVID-19, alongside other clinical and laboratory factors, is played by comorbidities.THE AIM OF THE STUDY. We studied the impact of comorbidities on the course and outcomes of severe COVID-19-associated pneumonia.MATERIAL AND METHODS. The study was conducted at the Yakut Republican Clinical Hospital. We analyzed treatment outcomes of 450 patients with severe COVID-19-associated pneumonia who were hospitalized in the intensive care unit. An observational case-control study was conducted, in accordance with the research objective, comorbidities were analyzed in detail in two groups of patients: survivors — 144 (32.0%) and deceased — 306 (68.0%). The endpoint of the study was a fatal outcome. The modified Charlson comorbidity index was used to assess the patients’ comorbidity status.RESULTS. The study revealed the presence of concomitant pathology in 446 (99.1%) patients. 57 (12.7%) patients had two concomitant diseases, 369 (82%) patients had three or more pathologies. A statistically significant impact on the risk of death for the following combinations of comorbid conditions were found: chronic central nervous system diseases with chronic kidney disease; hypertension with chronic kidney disease; coronary heart disease with chronic kidney disease; severe obesity (class III) with coronary heart disease and chronic kidney disease; severe obesity (class III) with type 2 diabetes mellitus. The mortality rate of patients increases linearly with the growth of the Charlson comorbidity index (p<0.001).CONCLUSION. The obtained data indicate a significant increase in the risk of death in patients with severe COVID-19-associated pneumonia in the presence of comorbidities. Therefore, when predicting the outcome and improving the treatment results of this category of patients, one should take into account the patient’s comorbidity.

Central Nervous System Involvement in Patients with Endogenous Endophthalmitis: A Retrospective Study

ABSTRACT Purpose The detrimental effects of endogenous endophthalmitis on visual acuity have been well studied; however, other complications of the central nervous system have not been robustly investigated. Our objective was to investigate central nervous system involvement associated with endogenous endophthalmitis. Methods We analyzed hospitalized patients with endogenous endophthalmitis in two hospitals from January 2010 to November 2020. We documented patient characteristics and outcomes related to endogenous endophthalmitis, including relevant neurologic complications. A neuroradiologist reviewed any available central nervous system imaging. Results A total of 62 patients were included (42 [68%] males and 20 [32%] female). Of those included, 14 patients (23%) had at least one neurologic complication associated with the central nervous system. Of those 14 patients, 8 (57%) had ischemic/embolic brain infarction(s), 7 (50%) had encephalopathy, 4 (29%) had cerebral hemorrhage(s), 2 (14%) had meningitis, 1 (7%) had a brain abscess, and 1 (7%) had an anoxic brain injury. Of the patients who had central nervous system complications, a majority of eight patients (57%) had positive blood cultures, two (14%) had positive intraocular cultures, while two (14%) were positive in both. There was no statistically significant difference in demographics, comorbidities, source of infection, or organism between patients with and without central nervous system complications. Conclusion The incidence of comorbid central nervous system disease in our cohort was higher than previously reported in the literature. Although we identified no specific risk factors for the development of central nervous system disease in endogenous endophthalmitis, we found that cases with more severe central nervous system complications were associated with culture positivity.

A Biomimetic Human Multi-Cellular In Vitro Model of the Blood-Brain Barrier.

Current in vitro models fail to recapitulate specific physiological properties of the human blood-brain barrier (BBB); hence the need for a reliable platform to study central nervous system diseases and drug permeability. To mimic the normally tight blood-brain interface, primary human endothelial cells (HAECs) and primary human astrocytes (A) were grown in a confined space of the physical scaffold created by gelatin methacrylate (GelMA) hydrogel to allow optimal astrocyte-endothelial cell direct/indirect interaction. Evidence for a physiologically relevant BBB was established by assessing the expression of tight junction markers conferring the barrier function, and by measuring biophysical attributes using the trans-endothelial electrical resistance (TEER) and the Evans blue albumin (EBA) permeability assay. An HAEC+A three-dimensional (3D) co-culture was associated with 12-fold higher claudin-5 (CLDN5) and cadherin-1 (CDH1 or Epithelial [E]-cadherin) transcriptional levels than two-dimensional (2D) models. This model conferred the highest TEER (45 Ω·cm2) in 3D HAEC+A, which value was 30 Ω·cm2 in 2D (p < 0.01) and 25 Ω·cm2 in 3D HAEC cultures (p < 0.001). Functionally, in 3D HAEC+A co-cultures, higher TEER resulted in 10-fold and 7-fold lower EBA permeability at 120 min, in HAECs alone or in to 2D co-cultures (p < 0.01). The established human primary cell model has acquired features mimicking the human BBB in vitro, and is now poised to be tested for the permeability of the BBB to pharmacological agents, parasites, cells (such as brain-tropic cancer cell metastasis) and any mechanisms that might involve traversing the BBB.

Neuroprotective effects of ghrelin in cuprizone-induced rat model of multiple sclerosis

Multiple sclerosis (MS) is an inflammatory central nervous system disease characterized by demyelination and axonal loss and is the main cause of non-traumatic neurological disability in young adults. Although there are several treatment approaches to manage the disease, there is no definitive cure for multiple sclerosis. Inflammation and oxidative stress are known to play important roles in the pathophysiology of MS. Ghrelin, a peptide secreted by the stomach, is reported to have neuroprotective properties through several pathways, including attenuating oxidative stress and inflammation. In the present study cuprizone (CPZ)-induced model of MS was used in Wistar albino rats to study the possible anti-inflammatory, antioxidant and neuroprotective effects of ghrelin. Rats were randomly divided into six groups: Control groups (Control35 and Control-S42), demyelination group, remyelination group, remyelination + ghrelin (20 µg/kg) group and remyelination + ghrelin (40 µg/kg) group. Y maze test was performed on the rats on their last day of the experiment. Oxidative stress and inflammatory parameters were investigated in brain using commercial kits by enzyme-linked immunosorbent assay (ELISA). Luxol fast blue (LFB) and hematoxylen&eosin (H&E) staining were performed in brain tissues. CPZ leads to a significant decrease in glutathione peroxidase (GSH-Px) levels and myelin content and a significant increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-ɑ), interleukin- 6 (IL- 6) levels, the number of lymphatic cells and inflammatory cells. A significant increase in the antioxidant parameter levels and a significant decrease in MDA levels were found in the ghrelin treated groups (p < 0.05). CPZ leads to irregular, fragmented, demyelinating nerve fibers. A more significant remyelination was observed in the ghrelin treated groups compared to the other groups (p < 0.05). In conclusion, ghrelin treatment showed neuroprotective and antioxidant properties and reduced demyelination in the CPZ-induced rat model of multiple sclerosis.Graphical

Breaking down barriers with sensory science-improving accessibility to neuroimmunology for the blind and low-vision communities.

Scientific public engagement activities and participation in bioscience discussions need to be open to everyone, as they play a significant role in connecting the general public to research and breaking down barriers of scientific skepticism. In a society increasingly shaped by scientific progress, it is crucial that everyone, regardless of their background or ability, feels empowered to participate in these conversations. However, this is not usually the case for blind or low-vision communities who are often excluded, in part due to scientific outreach events being historically limited to visual imagery. To break down such barriers, we organized a multisensory exhibition as part of the Cambridge Festival 2024. The initiative was inspired by Monash Sensory Science, a targeted outreach program designed to engage individuals who are blind, have low vision or diverse needs. Our aim was to use novel, tactile and informative models to explore the role of the immune system in the central nervous system health and disease, focusing on two inflammation models: traumatic brain injury and multiple sclerosis. In Sensory Science, we fostered the involvement of the blind and low-vision community through tactile scientific posters, resin and plaster brain models, and interactive experiences involving heat, sound, tactile poetry and photography. The Sensory Science exhibition held during March 2024 not only promoted equality but also reminded us that true innovation lies in the collective efforts of a diverse and inclusive community.

Glial fibrillary acidic protein: a potential biomarker for small fiber neuropathy?

Abstract Background Objective and easily applicable biomarkers for diabetic polyneuropathy (DPN) are warranted. Circulating nerve-specific proteins have emerged as valuable biomarkers for central nervous system disease but few of these have been tested in peripheral neuropathy. Glial Fibrillary Acidic Protein (GFAP) is highly expressed in non-myelinating Schwann cells while UCH-L1 is a neuron expressed stress protein not previous analyzed in DPN. In this pilot study, we explore serum GFAP and UCH-L1 levels in patients with/without DPN and controls. Methods Persons with DPN (n = 28), without DPN (n = 31), and controls (n = 30) were evaluated in a cross-sectional design. Sural nerve conduction (velocity and amplitude) was evaluated by NC-stat DPNCheck™ and quantitative sensory testing of cold detection and pain was performed. GFAP and UCH-L1 levels were compared across study groups and the unadjusted correlation with nerve assessments evaluated. Results Serum GFAP were lower in persons with DPN (20.9 ± 10.9 pg/ml) than in persons without DPN (26.2 ± 14.1 pg/ml) (p = 0.04) or controls (31.7 ± 26.0 pg/ml) (p = 0.02). GFAP levels were not different in persons without DPN and controls (p = 0.61). UCH-L1 levels were not different between study groups (p = 0.48). GFAP levels correlated with cold pain threshold (Rho= − 0.320, p = 0.02) but failed to reach significance for cold detection (Rho= − 0.236, p = 0.09). No correlation was observed between GFAP and nerve amplitude (p = 0.58) or conductivity (p = 0.86). Conclusion Serum GFAP levels are reduced in persons with DPN compared to persons without DPN and controls. Reduced serum GFAP levels may be associated with reduced markers of small nerve fiber damage obtained from quantitative sensory testing in people with diabetes.

Human neural stem cell-derived exosomes activate PINK1/Parkin pathway to protect against oxidative stress-induced neuronal injury in ischemic stroke

BackgroundMitochondria play a critical role in oxidative stress (OS)-induced neuronal injury during ischemic stroke (IS), making them promising therapeutic targets. Mounting evidence underscores the extraordinary therapeutic promise of exosomes derived from human neural stem cells (hNSCs) in the management of central nervous system (CNS) diseases. Nonetheless, the precise mechanisms by which these exosomes target mitochondria to ameliorate the effects of IS remain only partially elucidated. This study investigates the protective effects of hNSC derived exosomes (hNSC-Exos) on neuronal damage.MethodsUsing a rat model of middle cerebral artery occlusion (MCAO) in vivo and OS-induced HT22 cells in vitro. Firstly, our research group independently isolated human neural stem cells (hNSCs) and subsequently prepared hNSC-Exos. In vivo, MCAO rats were restored to blood flow perfusion to simulate ischemia–reperfusion injury, and hNSC-Exos were injected through stereotaxic injection into the brain. Subsequently, the protective effects of hNSC-Exos on MCAO rats were evaluated, including histological studies, behavioral assessments. In vivo, H2O2 was used in HT22 cells to simulate the OS environment in MCAO, and then its protective effects on HT22 were evaluated by co-culturing with hNSC-Exos, including immunofluorescence staining, western blotting (WB), quantitative real time PCR (qRT-PCR). In the process of exploring specific mechanisms, we utilized RNA sequencing (RNA-seq) to detect the potential induction of mitophagy in OS-induced HT22 cells. Afterwards, we employed a series of mitochondrial function assessments and autophagy related detection techniques, including measuring mitochondrial membrane potential, reactive oxygen species (ROS) levels, transmission electron microscopy (TEM) imaging, monodansylcadaverine (MDC) staining, and mCherry-GFP-LC3B staining. In addition, we further investigated the regulatory pathway of hNSC-Exos by using autophagy inhibitor mdivi-1 and knocking out PTEN induced kinase 1 (PINK1) in HT22 cells.ResultsAdministration of hNSC-Exos significantly ameliorated brain tissue damage and enhanced behavioral outcomes in MCAO rats. This treatment led to a reduction in brain tissue apoptosis and facilitated the normalization of impaired neurogenesis and neuroplasticity. Notably, the application of hNSC-Exos in vitro resulted in an upregulation of mitophagy in HT22 cells, thereby remedying mitochondrial dysfunction. We demonstrate that hNSC-Exos activate mitophagy via the PINK1/Parkin pathway, improving mitochondrial function and reducing neuronal apoptosis.ConclusionsThese findings suggest that hNSC-Exos alleviate OS-induced neuronal damage by regulating the PINK1/Parkin pathway. These reveals a novel role of stem cell-derived mitochondrial therapy in promoting neuroprotection and suggest their potential as a therapeutic approach for OS-associated CNS diseases, including IS.Graphical

A Bright Future for Photopharmaceuticals Addressing Central Nervous System Disorders: State of the Art and Challenges Toward Clinical Translation

ABSTRACTPhotopharmacology is an innovative approach that uses light to activate drugs. This method offers the potential for highly localized and precise drug activation, making it particularly promising for the treatment of neurological disorders. Despite the enticing prospects of photopharmacology, its application to treat human central nervous system (CNS) diseases remains to be demonstrated. In this review, we provide an overview of prominent strategies for the design and activation of photopharmaceutical agents in the field of neuroscience. Photocaged and photoswitchable drugs and bioactive molecules are discussed, and an instructive list of examples is provided to highlight compound design strategies. Special emphasis is placed on photoactivatable compounds for the modulation of glutamatergic, GABAergic, dopaminergic, and serotonergic neurotransmission for the treatment of neurological conditions, as well as various photoresponsive molecules with potential for improved pain management. Compounds holding promise for clinical translation are discussed in‐depth and their potential for future applications is assessed. Neurophotopharmaceuticals have yet to achieve breakthrough in the clinic, as both light delivery and drug design have not reached full maturity. However, by describing the current state of the art and providing illustrative case studies, we offer a perspective on future opportunities in the field of neurophotopharmacology focused on addressing CNS disorders.

Engineered endoplasmic reticulum-targeting nanodrugs with Piezo1 inhibition and promotion of cell uptake for subarachnoid hemorrhage inflammation repair

Subarachnoid hemorrhage (SAH) is a life-threatening acute hemorrhagic cerebrovascular condition, often presenting with severe headaches caused by intracranial hypertension, which in severe cases can lead to brain herniation. Piezo1 is a mechanosensitive ion channel protein whose mechanical properties are closely linked to central nervous system diseases. In this study, we developed an engineered endoplasmic reticulum membrane-based nanomedicine (CAQKERM@GsMTx4) using HEK293T cells, aimed at targeted delivery to acute hemorrhagic regions, rapid absorption, and precise inhibition of Piezo1 therapy. To ensure optimal targeting and therapeutic efficacy, we fused the CAQK peptide gene to the N-terminus of TRP-PK1, presenting the CAQK peptide on the endoplasmic reticulum membrane, and loaded GsMTx4 into engineered vesicles (EVs) derived from this engineered membrane. Through in vivo and in vitro experiments and multi-omics analysis, we have demonstrated the marked advantages of endoplasmic reticulum membrane vesicles over cell membrane-based vesicles. CAQKERM@GsMTx4 successfully inhibits Piezo1 in SAH, helps microglia change from the M1 phenotype to the M2 phenotype, and inhibits inflammatory responses and neuronal damage. Overall, this novel engineered endoplasmic reticulum membrane nanomedicine provides a potential effective strategy for the clinical treatment of subarachnoid hemorrhage.Graphical Engineered endoplasmic reticulum membrane-based nanomedicine, CAQKERM@GsMTx4, specifically targets hemorrhagic regions in subarachnoid hemorrhage (SAH). By inhibiting the Piezo1 ion channel, it promotes M2 microglial transformation, reducing inflammation and neuronal damage. This innovative approach leverages targeted delivery and precise modulation, offering a promising strategy for SAH treatment in both in vitro and in vivo models.

Air Pollution-Induced Neurotoxicity: The Relationship Between Air Pollution, Epigenetic Changes, and Neurological Disorders.

Air pollution is a major global health threat, responsible for over 8 million deaths in 2021, including 700,000 fatalities among children under the age of five. It is currently the second leading risk factor for mortality worldwide. Key pollutants, such as particulate matter (PM2.5, PM10), ozone, sulfur dioxide, nitrogen oxides, and carbon monoxide, have significant adverse effects on human health, contributing to respiratory and cardiovascular diseases, as well as neurodevelopmental and neurodegenerative disorders. Among these, particulate matter poses the most significant threat due to its highly complex mixture of organic and inorganic compounds with diverse sizes, compositions, and origins. Additionally, it can penetrate deeply into tissues and cross the blood-brain barrier, causing neurotoxicity which contributes to the development of neurodegenerative diseases. Although the link between air pollution and neurological disorders is well documented, the precise mechanisms and their sequence remain unclear. Beyond causing oxidative stress, inflammation, and excitotoxicity, studies suggest that air pollution induces epigenetic changes. These epigenetic alterations may affect the expression of genes involved in stress responses, neuroprotection, and synaptic plasticity. Understanding the relationship between neurological disorders and epigenetic changes induced by specific air pollutants could aid in the early detection and monitoring of central nervous system diseases.

Exome sequencing reveals low-frequency and rare variant contributions to multiple sclerosis susceptibility in Turkish families

Multiple sclerosis (MS) is characterized as an immune-mediated central nervous system disease marked by chronic inflammation, demyelination, and progressive neurodegeneration. In this study, we evaluated the contribution of low-frequency and rare genetic variants to MS susceptibility within one of the largest family-based MS cohorts to date, comprising 215 individuals from 59 Turkish multiplex MS families. Whole exome sequencing was conducted on all samples including affected and unaffected members, followed by investigation of the effect of well-established human leukocyte antigen loci for MS on the elevated MS risk observed in our families. Subsequently, a gene-based burden analysis was performed on candidate genes identified through both our segregation analysis and existing literature. To prioritize the genes and pathways that are potentially associated with MS, a segregation-based analysis of the variants was conducted and complemented by gene-based pathway enrichment analysis. Our results highlighted the significance of the extracellular matrix in MS pathogenesis, as we identified laminin-related genes including LAMA5 and LAMB1 from both the segregation analysis and gene-based burden test. Hemidesmosome assembly emerged as a key pathway in our analysis, primarily driven by the identification of DST and PLEC as significant genes in the gene-based segregation analysis. Finally, we identified two rare coding variants passing our allele frequency and deleteriousness score-based filters, rs41266745 (C> T) in the CD109 gene with CADD phred score 24 and rs143093165 (T> G) in the ITPR1 gene with CADD phred score 22 and LOEUF 0.325, segregating within more than one family. Overall, this is one of the first and largest family-based MS studies from Turkey that features a unique cohort from an admixed population that enabled the detection of novel low-frequency and rare variants associated with MS. The findings from this study offer valuable insights that could guide future research aimed at further exploring and understanding the factors contributing to MS risk.

GCN-BBB: Deep Learning Blood-Brain Barrier (BBB) Permeability PharmacoAnalytics with Graph Convolutional Neural (GCN) Network.

The Blood-Brain Barrier (BBB) is a selective barrier between the Central Nervous System (CNS) and the peripheral system, regulating the distribution of molecules. BBB permeability has been crucial in CNS-targeting drug development, such as glioblastoma-related drug discovery. In addition, more CNS diseases still present significant challenges, for instance, neurological disorders like Alzheimer's Disease (AD) and drug abuse. Conversely, cannabinoid drugs that do not cross the BBB are needed to avoid off-target CNS psychotropic effects. In vitro and in vivo experiments measuring BBB permeability are costly and low throughput. Computational pharmacoanalytics modeling, particularly using deep-learning Graph Neural Networks (GNNs), offers a promising alternative. GNNs excel at capturing intricate relationships in graph-based information, such as small molecular structures. In this study, we developed GNNs model for BBB permeability using the graph representation of drugs. The GNNs were compared with other algorithms using molecular fingerprints or physical-chemical descriptors. With a dataset of 1924 molecules, the best GNNs model, a convolutional graph neural network using a normalized Laplacian matrix (GCN_2), achieved a precision of 0.94, recall of 0.96, F1 score of 0.95, and MCC score of 0.77. This outperformed other machine learning algorithms with molecular fingerprints. The findings indicate that the graphic representation of small molecules combined with GNNs architecture is powerful in predicting BBB permeability with high accuracy and recall. The developed GNNs model can be utilized in the initial screening stage for new drug development.

New Dawn of Edible and Medicinal Fungi Unlocking Central Nervous System Diseases.

Central nervous system (CNS) diseases present unique clinical challenges characterized by insidious symptom onset, complex pathophysiology with incomplete mechanistic understanding, and substantial difficulties in therapeutic evaluation, thereby these inherent complexities create substantial obstacles for developing effective CNS diseases management strategies. Certain edible and medicinal fungi contain bioactive components, including polysaccharides, triterpenoids, alkaloids, and so on, which have therapeutic promise for CNS diseases. This paper reviews the current research advancements regarding the use of edible and medicinal fungi in the context of CNS diseases, highlighting their advantages as prospective therapeutic options and potential roles in both prevention and treatment. Through a comprehensive analysis of existing studies, the mechanisms and applications of these fungi are elucidated, providing valuable insights for the development of novel pharmaceuticals or functional foods aimed at combating CNS diseases.

Utilization of nanotechnology to surmount the blood-brain barrier in disorders of the central nervous system.

Utilization of nanotechnology to surmount the blood-brain barrier in disorders of the central nervous system.

Molecular mechanisms of Japanese encephalitis virus infection and advances in vaccine research.

Molecular mechanisms of Japanese encephalitis virus infection and advances in vaccine research.

Advances in Research on Exosomal miRNAs in Central Nervous System Diseases.

Neurological diseases present a wide range of conditions, intricate diagnosis and treatment processes, and complex prognostic considerations. Therefore, research focusing on the diagnosis and treatment of these diseases is crucial. Exosomal miRNAs are small RNA molecules enclosed in membrane vesicles, released by cells and known to play roles in the development of various neurological disorders. They also serve as specific biomarkers for these conditions. Drawing on extensive research on exosomal miRNAs in diseases like stroke, Alzheimer's, epilepsy, Parkinson's, and neuroregeneration, this paper provides a comprehensive review of the relationship between exosomal miRNAs and neurological diseases. We strive to offer current and detailed theoretical understandings to help with the diagnosis and treatment of these disorders.

Structure of myelin in the central nervous system and another possible driving force for its formation-myelin compaction.

Myelin formation is considered the last true "invention" in the evolution of vertebrate nervous system cell structure. The rapid jumping pulse propagation achieved by myelin enables the high conduction speed that is the basis of human movement, sensation, and cognitive function. As a key structure in the brain, white matter is the gathering place of myelin. However, with age, white matter-associated functions become abnormal and a large number of myelin sheaths undergo degenerative changes, causing serious neurological and cognitive disorders. Despite the extensive time and effort invested in exploring myelination and its functions, numerous unresolved issues and challenges persist. In-depth exploration of the functional role of myelin may bring new inspiration for the treatment of central nervous system (CNS) diseases and even mental illnesses. In this study, we conducted a comprehensive examination of the structure and key molecules of the myelin in the CNS, delving into its formation process. Specifically, we propose a new hypothesis regarding the source of power for myelin expansion in which membrane compaction may serve as a driving force for myelin extension. The implications of this hypothesis could provide valuable insights into the pathophysiology of diseases involving myelin malfunction and open new avenues for therapeutic intervention in myelin-related disorders.

Age-sensitive response of systemic AAV-mediated gene therapy in a newly characterized feline model of mucolipidosis II.

Age-sensitive response of systemic AAV-mediated gene therapy in a newly characterized feline model of mucolipidosis II.