{"title":"Rapamycin as a preventive intervention for Alzheimer's disease in APOE4 carriers: Targeting brain metabolic and vascular restoration.","authors":"Ai-Ling Lin, Chetan Aware","doi":"10.4103/NRR.NRR-D-24-01006","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-01006","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"21 2","pages":"685-686"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Polysialic acid-Siglec immune checkpoints of microglia and macrophages: Perspectives for therapeutic intervention.","authors":"Hauke Thiesler, Herbert Hildebrandt","doi":"10.4103/NRR.NRR-D-24-01195","DOIUrl":"10.4103/NRR.NRR-D-24-01195","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"661-662"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mei Liu, Yijing Meng, Siguang Ouyang, Meng'ai Zhai, Likun Yang, Yang Yang, Yuhai Wang
{"title":"Neuromodulation technologies improve functional recovery after brain injury: From bench to bedside.","authors":"Mei Liu, Yijing Meng, Siguang Ouyang, Meng'ai Zhai, Likun Yang, Yang Yang, Yuhai Wang","doi":"10.4103/NRR.NRR-D-24-00652","DOIUrl":"10.4103/NRR.NRR-D-24-00652","url":null,"abstract":"<p><p>Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited. This limited plasticity serves as a primary barrier to functional recovery after brain injury. Neuromodulation technologies represent one of the fastest-growing fields in medicine. These techniques utilize electricity, magnetism, sound, and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury. Therefore, this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury. Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury. However, studies report negative findings, potentially due to variations in stimulation protocols, differences in observation periods, and the severity of functional impairments among participants across different clinical trials. Additionally, we observed that different neuromodulation techniques share remarkably similar mechanisms, including promoting neuroplasticity, enhancing neurotrophic factor release, improving cerebral blood flow, suppressing neuroinflammation, and providing neuroprotection. Finally, considering the advantages and disadvantages of various neuromodulation techniques, we propose that future development should focus on closed-loop neural circuit stimulation, personalized treatment, interdisciplinary collaboration, and precision stimulation.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"506-520"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"p21 as an essential regulator of neurogenic homeostasis in neuropathological conditions.","authors":"Valentina Mastrorilli, Stefano Farioli-Vecchioli","doi":"10.4103/NRR.NRR-D-24-01255","DOIUrl":"10.4103/NRR.NRR-D-24-01255","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"675-676"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongli Chen, Na Li, Yuanhao Cai, Chunyan Ma, Yutong Ye, Xinyu Shi, Jun Guo, Zhibo Han, Yi Liu, Xunbin Wei
{"title":"Exosomes in neurodegenerative diseases: Therapeutic potential and modification methods.","authors":"Hongli Chen, Na Li, Yuanhao Cai, Chunyan Ma, Yutong Ye, Xinyu Shi, Jun Guo, Zhibo Han, Yi Liu, Xunbin Wei","doi":"10.4103/NRR.NRR-D-24-00720","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-00720","url":null,"abstract":"<p><p>In recent years, exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research. Exosomes are small and can effectively cross the blood-brain barrier, allowing them to target deep brain lesions. Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines, mRNAs, and disease-related proteins, thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects. However, exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells. This limitation can lead to side effects and toxicity when they interact with non-specific cells. Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases. In this review, we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases. Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases. We introduce the strategies being used to enhance exosome targeting, including genetic engineering, chemical modifications (both covalent, such as click chemistry and metabolic engineering, and non-covalent, such as polyvalent electrostatic and hydrophobic interactions, ligand-receptor binding, aptamer-based modifications, and the incorporation of CP05-anchored peptides), and nanomaterial modifications. Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases. However, several challenges remain in the clinical application of exosomes. Improvements are needed in preparation, characterization, and optimization methods, as well as in reducing the adverse reactions associated with their use. Additionally, the range of applications and the safety of exosomes require further research and evaluation.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"21 2","pages":"478-490"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Topical administration of GLP-1 eyedrops improves retinal ganglion cell function by facilitating presynaptic GABA release in early experimental diabetes.","authors":"Yu-Qi Shao, Yong-Chen Wang, Lu Wang, Hang-Ze Ruan, Yun-Feng Liu, Ti-Hui Zhang, Shi-Jun Weng, Xiong-Li Yang, Yong-Mei Zhong","doi":"10.4103/NRR.NRR-D-24-00001","DOIUrl":"10.4103/NRR.NRR-D-24-00001","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202602000-00048/figure1/v/2025-05-05T160104Z/r/image-tiff Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell loss contributing to visual dysfunction or blindness. In the brain, defects in γ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells. In the present study, we used the patch-clamp technique to record γ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats. We found that early diabetes (4 weeks of hyperglycemia) decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude, suggesting a reduction in the spontaneous release of γ-aminobutyric acid to retinal ganglion cells. Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency, subsequently enhancing the survival of retinal ganglion cells. Concurrently, the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39, a specific glucagon-like peptide-1 receptor antagonist, or SR95531, a specific antagonist of the γ-aminobutyric acid subtype A receptor. Furthermore, extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON- and OFF-type retinal ganglion cells. This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca 2+ /protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation. Moreover, multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells. Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1. These results suggest that glucagon-like peptide-1 facilitates the release of γ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor, leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy. Collectively, our findings indicate th","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"800-810"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Specific dendritic spine modifications and dendritic transport: From in vitro to in vivo.","authors":"Albert H K Fok, Charlotte H M Lam, Cora S W Lai","doi":"10.4103/NRR.NRR-D-24-01159","DOIUrl":"10.4103/NRR.NRR-D-24-01159","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"665-666"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sox2-overexpressing neural stem cells alleviate ventricular enlargement and neurological dysfunction in posthemorrhagic hydrocephalus.","authors":"Baocheng Gao, Haoxiang Wang, Shuang Hu, Kunhong Zhong, Xiaoyin Liu, Ziang Deng, Yuanyou Li, Aiping Tong, Liangxue Zhou","doi":"10.4103/NRR.NRR-D-24-01491","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-01491","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202602000-00045/figure1/v/2025-05-05T160104Z/r/image-tiff Neural stem cells (NSCs) have the potential for self-renewal and multidirectional differentiation, and their transplantation has achieved good efficacy in a variety of diseases. However, only 1%-10% of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus. Sox2 is an important factor for NSCs to maintain proliferation. Therefore, Sox2-overexpressing NSCs (NSCSox2) may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus. In this study, human NSCSox2 was transplanted into a posthemorrhagic hydrocephalus mouse model, and retinoic acid was administered to further promote NSC differentiation. The results showed that NSCSox2 attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function. NSCSox2 also promoted nerve regeneration, inhibited neuroinflammation and promoted M2 polarization (anti-inflammatory phenotype), thereby reducing cerebrospinal fluid secretion in choroid plexus. These findings suggest that NSCSox2 rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"21 2","pages":"769-779"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanwen Cao, Li Shang, Deheng Hu, Jianbing Huang, Yu Wang, Ming Li, Yilin Song, Qianzi Yang, Yan Luo, Ying Wang, Xinxia Cai, Juntao Liu
{"title":"Neuromodulation techniques for modulating cognitive function: Enhancing stimulation precision and intervention effects.","authors":"Hanwen Cao, Li Shang, Deheng Hu, Jianbing Huang, Yu Wang, Ming Li, Yilin Song, Qianzi Yang, Yan Luo, Ying Wang, Xinxia Cai, Juntao Liu","doi":"10.4103/NRR.NRR-D-24-00836","DOIUrl":"10.4103/NRR.NRR-D-24-00836","url":null,"abstract":"<p><p>Neuromodulation techniques effectively intervene in cognitive function, holding considerable scientific and practical value in fields such as aerospace, medicine, life sciences, and brain research. These techniques utilize electrical stimulation to directly or indirectly target specific brain regions, modulating neural activity and influencing broader brain networks, thereby regulating cognitive function. Regulating cognitive function involves an understanding of aspects such as perception, learning and memory, attention, spatial cognition, and physical function. To enhance the application of cognitive regulation in the general population, this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions. This review covers various neuromodulation techniques for cognitive intervention, including deep brain stimulation, vagus nerve stimulation, and invasive methods using microelectrode arrays. The non-invasive techniques discussed include transcranial magnetic stimulation, transcranial direct current stimulation, transcranial alternating current stimulation, transcutaneous electrical acupoint stimulation, and time interference stimulation for activating deep targets. Invasive stimulation methods, which are ideal for studying the pathogenesis of neurological diseases, tend to cause greater trauma and have been less researched in the context of cognitive function regulation. Non-invasive methods, particularly newer transcranial stimulation techniques, are gentler and more appropriate for regulating cognitive functions in the general population. These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets. This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology. It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation. Additionally, researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"491-501"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}