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{"title":"NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation.","authors":"Zhihao Lin, Changzhou Ying, Xiaoli Si, Naijia Xue, Yi Liu, Ran Zheng, Ying Chen, Jiali Pu, Baorong Zhang","doi":"10.4103/NRR.NRR-D-23-01265","DOIUrl":"10.4103/NRR.NRR-D-23-01265","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202507000-00026/figure1/v/2024-09-09T124005Z/r/image-tiff Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta. Ferroptosis, a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation, plays a vital role in the death of dopaminergic neurons. However, the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated. NADPH oxidase 4 is related to oxidative stress, however, whether it regulates dopaminergic neuronal ferroptosis remains unknown. The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis, and if so, by what mechanism. We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model. NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons. Moreover, NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals. Mechanistically, we found that NADPH oxidase 4 interacted with activated protein kinase C α to prevent ferroptosis of dopaminergic neurons. Furthermore, by lowering the astrocytic lipocalin-2 expression, NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation. These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation, which contribute to dopaminergic neuron death, suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":"2038-2052"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into spinal muscular atrophy from molecular biomarkers.","authors":"Xiaodong Xing, Xinzhu Liu, Xiandeng Li, Mi Li, Xian Wu, Xiaohui Huang, Ajing Xu, Yan Liu, Jian Zhang","doi":"10.4103/NRR.NRR-D-24-00067","DOIUrl":"10.4103/NRR.NRR-D-24-00067","url":null,"abstract":"<p><p>Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness. It is one of the most common genetic causes of mortality among infants aged less than 2 years. Biomarker research is currently receiving more attention, and new candidate biomarkers are constantly being discovered. This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons. We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy, which are classified as either specific or non-specific biomarkers. This review provides new insights into the pathogenesis of spinal muscular atrophy, the mechanism of biomarkers in response to drug-modified therapies, the selection of biomarker candidates, and would promote the development of future research. Furthermore, the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":"1849-1863"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease.","authors":"Gabriela Seplovich, Yazan Bouchi, Juan Pablo de Rivero Vaccari, Jennifer C Munoz Pareja, Andrew Reisner, Laura Blackwell, Yehia Mechref, Kevin K Wang, J Adrian Tyndall, Binu Tharakan, Firas Kobeissy","doi":"10.4103/NRR.NRR-D-24-00107","DOIUrl":"10.4103/NRR.NRR-D-24-00107","url":null,"abstract":"<p><p>Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasome-dependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":"20 6","pages":"1644-1664"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of exercise-hormone irisin in Alzheimer's disease.","authors":"Eunhee Kim, Rudolph E Tanzi, Se Hoon Choi","doi":"10.4103/NRR.NRR-D-24-00098","DOIUrl":"10.4103/NRR.NRR-D-24-00098","url":null,"abstract":"<p><p>Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type III domain-containing protein 5 (FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":"1555-1564"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphodiesterase 9 localization in cytoplasm and nucleus: the gateway to selective targeting in neuroprotection?","authors":"Giovanni Ribaudo, Matteo Giannangeli, Margrate Anyanwu, Alessandra Gianoncelli","doi":"10.4103/NRR.NRR-D-24-00373","DOIUrl":"10.4103/NRR.NRR-D-24-00373","url":null,"abstract":"","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":"20 6","pages":"1701-1702"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell and spatial omics: exploring hypothalamic heterogeneity.","authors":"Muhammad Junaid, Eun Jeong Lee, Su Bin Lim","doi":"10.4103/NRR.NRR-D-24-00231","DOIUrl":"10.4103/NRR.NRR-D-24-00231","url":null,"abstract":"<p><p>Elucidating the complex dynamic cellular organization in the hypothalamus is critical for understanding its role in coordinating fundamental body functions. Over the past decade, single-cell and spatial omics technologies have significantly evolved, overcoming initial technical challenges in capturing and analyzing individual cells. These high-throughput omics technologies now offer a remarkable opportunity to comprehend the complex spatiotemporal patterns of transcriptional diversity and cell-type characteristics across the entire hypothalamus. Current single-cell and single-nucleus RNA sequencing methods comprehensively quantify gene expression by exploring distinct phenotypes across various subregions of the hypothalamus. However, single-cell/single-nucleus RNA sequencing requires isolating the cell/nuclei from the tissue, potentially resulting in the loss of spatial information concerning neuronal networks. Spatial transcriptomics methods, by bypassing the cell dissociation, can elucidate the intricate spatial organization of neural networks through their imaging and sequencing technologies. In this review, we highlight the applicative value of single-cell and spatial transcriptomics in exploring the complex molecular-genetic diversity of hypothalamic cell types, driven by recent high-throughput achievements.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":"1525-1540"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The complex roles of m 6 A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases.","authors":"Yanxi Li, Jing Xue, Yuejia Ma, Ke Ye, Xue Zhao, Fangliang Ge, Feifei Zheng, Lulu Liu, Xu Gao, Dayong Wang, Qing Xia","doi":"10.4103/NRR.NRR-D-23-01872","DOIUrl":"10.4103/NRR.NRR-D-23-01872","url":null,"abstract":"<p><p>N6-methyladenosine (m 6 A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m 6 A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m 6 A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m 6 A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m 6 A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m 6 A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m 6 A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m 6 A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m 6 A's role in neurodegenerative processes. The roles of m 6 A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the time-specific nature of m 6 A and its varying effects on distinct brain regions and in different environments.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":"1582-1598"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential mechanism and clinical application value of remote ischemic conditioning in stroke.","authors":"Yajun Zhu, Xiaoguo Li, Xingwei Lei, Liuyang Tang, Daochen Wen, Bo Zeng, Xiaofeng Zhang, Zichao Huang, Zongduo Guo","doi":"10.4103/NRR.NRR-D-23-01800","DOIUrl":"10.4103/NRR.NRR-D-23-01800","url":null,"abstract":"<p><p>Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":"1613-1627"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging-induced memory loss due to decreased N1-acetyl-5-methoxykynuramine, a melatonin metabolite, in the hippocampus: a potential prophylactic agent for dementia.","authors":"Kazuki Watanabe, Atsuhiko Hattori","doi":"10.4103/NRR.NRR-D-24-00379","DOIUrl":"10.4103/NRR.NRR-D-24-00379","url":null,"abstract":"","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":"20 6","pages":"1705-1706"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights from an academic endeavor into central nervous system drug discovery.","authors":"Lieve van Veggel, An M Voets, Tim Vanmierlo, Rudy Schreiber","doi":"10.4103/NRR.NRR-D-24-00340","DOIUrl":"10.4103/NRR.NRR-D-24-00340","url":null,"abstract":"","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":"20 6","pages":"1717-1718"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}