Cellular and Molecular Neurobiology最新文献

Peripheral nerve injuries (PNIs) remain a major cause of long-term disability, with standard treatments such as microsurgical repair and autologous grafting often yielding incomplete recovery due to slow axonal regeneration, fibrotic scarring, and limited reinnervation. Emerging therapies, including electrical stimulation (ES) and platelet-rich plasma (PRP), have shown promise but remain insufficient as standalone interventions. ES enhances axonal elongation, remyelination, and neuroplasticity by upregulating regeneration-associated genes and neurotrophins, while PRP delivers autologous growth factors that promote angiogenesis, Schwann cell activation, immunomodulation, and antioxidant defense. Both therapies converge on shared pathways by reducing inflammation, oxidative stress, and scar formation, thereby remodeling the microenvironment into a pro-regenerative niche. Preclinical evidence indicates that combining ES and PRP provides complementary benefits, with ES priming the injury site and PRP sustaining trophic support, resulting in superior axonal density, myelination, and functional recovery compared to monotherapies. Future directions emphasize personalized protocols, optimized ES parameters, standardized PRP formulations, and integration with biomaterials and closed-loop stimulation systems. Translation to clinical practice, however, requires standardized guidelines and rigorous randomized controlled trials to validate these multimodal strategies and enable patient-specific regenerative therapies.

Glioblastoma is a lethal primary brain tumor with poor prognosis. Tumor cells exhibit substantial phenotypic variation, complicating treatment. As functional diversity is driven by underlying transcriptional states, characterizing tumor cell gene expression is essential for understanding tumor biology and therapeutic response. The GL261 tumor cell line is a common pre-clinical model system for investigating glioblastoma pathobiology. However, global gene expression patterns in this model are unknown. Here we describe the use of single-cell RNA sequencing (scRNA-Seq) to investigate transcriptional profiles of 5764 adherent and 4951 neurosphere GL261 cells, generating 133,442,221 sequenced reads. Following Principal Component Analysis (PCA) for dimensionality reduction, we applied Uniform Manifold Approximation and Projection (UMAP) to visualize transcriptionally distinct subpopulations (clusters) of GL261 cells grown adherently or as neurospheres. Highly expressed and differentially expressed genes were identified. Because the neurosphere phenotype is known to be more tumorigenic, we further examined differentially expressed genes with gene ontology expression analysis. We found that upregulated genes in neurosphere cells are associated with angiogenesis, cell adhesion, and cell signaling pathways. In addition, we specifically examined gene expression patterns of matrix metalloproteinases and purinergic receptors, glioblastoma drug targets known to be important for promoting tumor infiltration into adjacent healthy tissue. We found that P2RX7, MMP15 and MMP16 are upregulated in neurosphere cells, indicating a potential role for these genes in tumor formation. Together these results reveal global transcriptional profiles of GL261 cells, establish a resource for further scRNA-Seq-based analyses, and give insight into gene expression changes relevant to glioblastoma tumor development.

Lesch-Nyhan disease (LND) is an ultra-rare X-linked inborn error of metabolism caused by complete or partial deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT), a key enzyme in the purine salvage pathway. This defect leads to uric acid overproduction and a broad spectrum of neurological and behavioral manifestations, whose severity depends on the degree of residual enzymatic activity. Although emerging evidence implicates HPRT deficiency in widespread cellular dysfunctions, particularly within midbrain dopaminergic neurons, the molecular mechanisms underlying the neurobehavioral phenotype of HPRT deficiency remain poorly understood and are not adequately explained by purine metabolism dysfunctions alone. Although proteomics represents a powerful approach for elucidating molecular alterations underlying disease, it has so far found only limited application in LND research. To address this gap, we provide here the first proteomic study combined with clinical biochemistry data and pro-inflammatory cytokines profiling of plasma samples from 29 HPRT deficient individuals (21 with classic LND and 8 with Lesch-Nyhan variants - LNV). We suggest that plasma proteomics might be a potential tool in LND for monitoring disease progression and therapeutic response, potentially paving the way for targeted treatment strategies that extend beyond the purine salvage pathway to address the currently unmet clinical needs of LND patients.

Alzheimer's disease (AD) is a neurodegenerative disease closely associated with age. The main clinical manifestations include cognitive impairment, including visuospatial ability, memory, language, and behavioral disorders. These manifestations considerably impair the patients' ability to perform daily activities. Although the pathogenesis of AD remains unclear, many studies have confirmed the essential role of abnormal lipid metabolism and inflammatory response in AD occurrence and progression. In this review, based on the relationship between lipid metabolism disorders and neuroinflammation, the regulatory mechanism of lipid mediators, and the role of microglia, we systematically discuss how lipid metabolism affects the pathological process of AD by regulating the inflammatory response.

Spinal cord injury (SCI) is one of the most common critical illnesses, which can cause neurological deficits and disabilities of motor, sensory and autonomic nervous system in mild cases, and lead to paralysis or even death following severe trauma. Although there are currently no effective and satisfactory clinical treatments, the efforts for repair SCI never stop. Besides the traditional strategies such as drugs, surgical interventions and rehabilitative care, the bionic therapies have attracted significant attention due to its considerable promise. The bionic therapies for SCI mainly included engineered biomaterials-based approaches aiming for reconstruction of internal neural circuit and brain machine interfaces (BMI)-based technologies to integrate extrinsic control and intrinsic circuit. This review provides an extensive overview of SCI research and bionic therapies, with focus on reconstruction and integration of neural circuit, which might provide promising insights on clinical treatment.

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Extracellular senile plaques composed of amyloid-β (Aβ) peptides, intracellular neurofibrillary tangles (NFTs) containing the hyperphosphorylated tau protein, excessive production of reactive oxygen species (ROS) and neuroinflammation are crucial contributing factors to the pathological mechanisms of AD. The nonreceptor tyrosine kinase c-Abl plays a complex dual role in AD through the regulation of signaling pathways such as oxidative stress, DNA repair, and apoptosis. c-Abl mitigates early neuronal damage by activating antioxidant enzymes and potentially promoting homologous recombination (HR) repair. However, its aberrant activation is associated with Aβ plaque formation, tau phosphorylation, neuronal cell death, and synaptic dysfunction. Its synergistic interaction with Aβ and tau exacerbates the neurodegenerative pathology. This article provides a systematic review of the molecular mechanisms of c-Abl in AD, including its dual role in oxidative stress, synergistic regulation of neuronal function with Aβ and the tau protein, involvement in the maintenance of genomic stability, and potential as a therapeutic target.

Gliomas are complex and among the most lethal central nervous system (CNS) disorders. While they are notoriously heterogeneous, evidences suggest critical involvement of intricate interactions between RNA-binding proteins (RBPs) and their diverse partners, in the pathogeneses of gliomas. In this study, we used RNA sequencing data from the Cancer Genome Atlas (TCGA) to identify differentially expressed genes (DEGs). After selection of differentially expressed RBPs from these DEGs, systematic investigation of their transcriptomic changes during glioma progression was undertaken. Extensive in silico assessments allowed the creation of their interactome and pathway, identifying potential biological effects of these differentially expressed RBPs. Construction of regulatory networks of these differentially expressed RBPs and their topological analysis discovered key RBPs such as PABPC1, EIF4A2, RPS3, EEF1A1, RPS6, ELAVL2, CPEB1, and CELF5, which are largely involved in alternative splicing and ribosomal biogenesis. Moreover, we also identified differentially expressed RBPs such as YBX1, ELAVL2, and IGF2BP1, which may be involved in the formation of stress granules in gliomas. We also identified highly mutated RBPs, such as RPSA, RPL5, CPEB4, and SMAD7, in gliomas. Further, RBPs like RPS8, RPL5, RPS3A, EEF1A1, and EIF4E1B were found to be strongly correlated with patients' overall survival. Taken together, our analyses identified several candidate RBPs which might serve as potential targets for oncological measures against gliomas.

The parasympathetic nervous system (PNS), a division of the autonomic nervous system, maintains physiological homeostasis within the body. The PNS seems to influence the processing of nociceptive information. A growing body of research indicates that the PNS actively contributes to various pain conditions associated with inflammation of tissues and/or neural damage. Therefore, the aim of this review is to integrate current findings regarding the peripheral parasympathetic pathways implicated in pain, encompassing direct cholinergic actions and indirect effects on the sensory nervous system. Enhanced insight into PNS-sensory interactions in pain could provide a basis for identifying new strategies for the prevention and management of pain conditions.

The interaction between lipid droplet (LD) metabolism and immune polarisation of microglia after stroke plays a key role in the regulation of neuroinflammation and tissue repair. This review analysed the molecular mechanism, spatiotemporal specificity, and the dual role of the LD metabolism-immune axis in microglia after stroke. Microglial LDs can dynamically store neutral lipids and regulate the metabolite-immune network, playing a protective role in the early stage of stroke by isolating pro-inflammatory precursors, inhibiting oxidative stress and iron death, and maintaining energy buffer. Spatiotemporal analysis revealed significant heterogeneity in the distribution and function of LDs across different stages of stroke and in distinct brain areas (infarct core, peri-infarct region, and non-infarct area), directly correlating with the pro-inflammatory/anti-inflammatory phenotypic transformation of microglia. The development of LD-related biomarkers (such as near-infrared imaging), the repurpose of peroxisome proliferator-activated receptor γ agonists (rosiglitazone) and HDAC inhibitors (volinostat), as well as the design of novel drugs (such as Triggering Receptor Expressed on Myeloid Cells 2 agonists and perilipin 2 small interfering RNA) are expected to improve stroke outcomes by transforming metabolic homeostasis and immune balance. Multi-omics technology and intelligent delivery system should be combined to overcome the limitations of the blood-brain barrier, promote the clinical transformation of the "metabolism-immunity" collaborative intervention strategy, and provide a new paradigm for precision treatment of stroke.