全部最新文献

The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity, oxidative stress, inflammatory responses, and blood-brain barrier disruption. While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success, reperfusion injury remains a significant contributor to the exacerbation of brain injury. This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury. The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke, covering research progress in nanoparticle-based drug delivery, targeted therapy, and antioxidant and anti-inflammatory applications. Nano-based drug delivery systems offer several advantages compared to traditional therapies, including enhanced blood-brain barrier penetration, prolonged drug circulation time, improved drug stability, and targeted delivery. For example, inorganic nanoparticles, such as those based on CeO 2 , have been widely studied for their strong antioxidant capabilities. Biomimetic nanoparticles, such as those coated with cell membranes, have garnered significant attention owing to their excellent biocompatibility and targeting abilities. Nanoparticles can be used to deliver a wide range of neuroprotective agents, such as antioxidants (e.g., edaravone), anti-inflammatory drugs (e.g., curcumin), and neurotrophic factors. Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions. Although nanotechnology has demonstrated great potential in animal studies, its clinical application still faces several challenges, including the long-term safety of nanoparticles, the feasibility of large-scale production, quality control, and the ability to predict therapeutic effects in humans. In summary, nanotechnology holds significant promise for the treatment of ischemic stroke. Future research should focus on further exploring the mechanisms of action of nanoparticles, developing multifunctional nanoparticles, and validating their safety and efficacy through rigorous clinical trials. Moreover, interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.

Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions. They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage. The main types include amyotrophic lateral sclerosis, progressive muscular atrophy, primary lateral sclerosis, and progressive bulbar palsy, the pathological processes of which are largely identical, with the main disparity lying in the location of the lesions. Amyotrophic lateral sclerosis is the representative condition in this group of diseases, while other types are its variants. Hence, this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases. Although the precise pathogenesis remains elusive, recent advancements have shed light on various theories, including gene mutation, excitatory amino acid toxicity, autoimmunology, and neurotrophic factors. The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis: riluzole, edaravone, AMX0035, and tofersen, with the latter being the most recent to receive approval. However, following several phase III trials that failed to yield favorable outcomes, AMX0035 has been voluntarily withdrawn from both the US and Canadian markets. This article presents a comprehensive summary of drug trials primarily completed between January 1, 2023, and June 30, 2024, based on data sourced from clinicaltrials.gov. Among these trials, five are currently in phase I, seventeen are in phase II, and eleven are undergoing phase III evaluation. Notably, 24 clinical trials are now investigating potential disease-modifying therapy drugs, accounting for the majority of the drugs included in this review. Some promising drugs being investigated in preclinical studies, such as ATH-1105, are included in our analysis, and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases. This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs, with the aim of highlighting the latest potentialities for clinical therapy.

Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration. Viral pathogens or their products can invade the central nervous system and cause damage, leading to meningitis, encephalitis, meningoencephalitis, myelitis, or post-infectious demyelinating diseases. Although neuroinflammation initially has a protective function, chronic inflammation can contribute to the development of neurodegenerative diseases. Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis, respectively. Extracellular nucleotides, particularly adenosine triphosphate and its metabolites are released from activated, infected, and dying cells, acting as alarmins mediating neuroinflammation and neurodegeneration. When viruses infect central nervous system cells, adenosine triphosphate is released as an alarmin, triggering inflammatory responses. This process is mediated by purinergic receptors, divided into two families: P1, which responds to adenosine, and P2, activated by adenosine triphosphate and other nucleotides. This review highlights how specific viruses, such as human immunodeficiency virus type 1, Theiler's murine encephalomyelitis virus, herpes simplex virus type 1, Epstein-Barr virus, dengue virus, Zika virus, and severe acute respiratory syndrome coronavirus 2, can initiate inflammatory responses through the release of extracellular nucleotides, particularly adenosine triphosphate, which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders. A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.

JOURNAL/nrgr/04.03/01300535-202605000-00040/figure1/v/2025-10-21T121913Z/r/image-tiff Peripheral nerve defect repair is a complex process that involves multiple cell types; perineurial cells play a pivotal role. Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling; however, their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection, which are similar to the risks associated with other stem cell transplantations. The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells, which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks. In vitro , small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation, migration, tube formation, and barrier function of perineurial cells, and subsequently upregulated the expression of tight junction proteins. Furthermore, in a rat model of sciatic nerve defects bridged with silicon tubes, treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells, thus facilitating neural tissue regeneration. At 10 weeks post-surgery, rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy. Transcriptomic and microRNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver miR-21-5p, which inhibits mothers against decapentaplegic homolog 7 expression, thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression, and further enhancing tight junction protein expression. Together, our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation, migration, and tight junction protein formation of perineurial cells. These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells, and present a novel approach for the clinical treatment of peripheral nerve defects.

JOURNAL/nrgr/04.03/01300535-202605000-00036/figure1/v/2025-10-21T121913Z/r/image-tiff Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions. However, the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear. Long non-coding RNAs (lncRNAs) have been shown to influence the occurrence and development of these lesions. We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing. To investigate the mechanism by which lnc_011797 regulates white matter lesions, we established subjected human umbilical vein endothelial cells to oxygen-glucose deprivation to simulate conditions associated with white matter lesions. The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses. Our findings indicate that lnc_011797 promoted ferroptosis in these cells, leading to the formation of white matter lesions. Furthermore, lnc_011797 functioned as a competitive endogenous RNA (ceRNA) for miR-193b-3p, thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins. To validate the role of lnc_011797 in vivo , we established a mouse model of white matter lesions through bilateral common carotid artery stenosis. The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions. These findings clarify the mechanism by which lncRNAs regulate white matter lesions, providing a new target for the diagnosis and treatment of white matter lesions.

Spinal cord injury is a severe neurological disorder; however, current treatment methods often fail to restore nerve function effectively. Spinal cord stimulation via electrical signals is a promising therapeutic modality for spinal cord injury. Based on similar principles, this review aims to explore the potential of optical and acoustic neuromodulation techniques, emphasizing their benefits in the context of spinal cord injury. Photoacoustic imaging, renowned for its noninvasive nature, high-resolution capabilities, and cost-effectiveness, is well recognized for its role in early diagnosis, dynamic monitoring, and surgical guidance in stem cell therapies for spinal cord injury. Moreover, photoacoustodynamic therapy offers multiple pathways for tissue regeneration. Optogenetics and sonogenetics use genetic engineering to achieve precise neuronal activation, while photoacoustoelectric therapy leverages photovoltaic materials for electrical modulation of the nervous system, introducing an innovative paradigm for nerve system disorder management. Collectively, these advancements represent a transformative shift in the diagnosis and treatment of spinal cord injury, with the potential to significantly enhance nerve function remodeling and improve patient outcomes.

JOURNAL/nrgr/04.03/01300535-202605000-00041/figure1/v/2025-10-21T121913Z/r/image-tiff Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death. Although extensive research has been conducted on neuroprotection for retinal ganglion cells, there is still no treatment for clinical use. Recent evidence shows that extracellular vesicles isolated from a variety of stem cells are efficacious in retinal ganglion cell neuroprotection. In this study, we tested the novel extracellular vesicle source of the retinal progenitor R-28 cell line in vitro and in vivo . We isolated and characterized extracellular vesicles from R-28 cells and tested their therapeutic efficacy in terms of retinal ganglion cell survival in vitro and in an in vivo glaucoma model, measuring retinal ganglion cell survival and preservation of their axons. Additionally, we tested extracellular vesicles for their neuroprotective capacity in retinal ganglion cells differentiated from human embryonic stem cells. Finally, we investigated miRNA changes in retinal ganglion cells with R-28 extracellular vesicle treatment, and predicted possible pathways that may be modulated. R-28 extracellular vesicles improved retinal ganglion cell survival but failed to preserve axons significantly. Moreover, the results also illustrated the neuroprotection of R-28 extracellular vesicles on human retinal ganglion cells. Finally, we also showed changes in hsa-miRNA-4443, hsa-miRNA-216a-5p, hsa-let-7e-5p, hsa-miRNA-374b-5p, hsa-miRNA-331-3p, and hsa-miRNA-421 expressions, which may have neuroprotective potential on retinal ganglion cell degeneration. This study will pave the way for miRNA and extracellular vesicle-based neuroprotective therapies for glaucoma.