Zoological Research最新文献

{"title":"Bat-derived oligopeptide LE6 inhibits the contact-kinin pathway and harbors anti-thromboinflammation and stroke potential.","authors":"Li-Na Cha, Juan Yang, Jin-Ai Gao, Xin Lu, Xiao-Long Chang, Rebecca Caroline Thuku, Qi Liu, Qiu-Min Lu, Dong-Sheng Li, Ren Lai, Ming-Qian Fang","doi":"10.24272/j.issn.2095-8137.2023.372","DOIUrl":"10.24272/j.issn.2095-8137.2023.372","url":null,"abstract":"<p><p>Thrombosis and inflammation are primary contributors to the onset and progression of ischemic stroke. The contact-kinin pathway, initiated by plasma kallikrein (PK) and activated factor XII (FXIIa), functions bidirectionally with the coagulation and inflammation cascades, providing a novel target for therapeutic drug development in ischemic stroke. In this study, we identified a bat-derived oligopeptide from <i>Myotis myotis</i> (Borkhausen, 1797), designated LE6 (Leu-Ser-Glu-Glu-Pro-Glu, 702 Da), with considerable potential in stroke therapy due to its effects on the contact kinin pathway. Notably, LE6 demonstrated significant inhibitory effects on PK and FXIIa, with inhibition constants of 43.97 μmol/L and 6.37 μmol/L, respectively. <i>In vitro</i> analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin time. In murine models, LE6 effectively inhibited carrageenan-induced mouse tail thrombosis, FeCl ₃-induced carotid artery thrombosis, and photochemically induced intracerebral thrombosis. Furthermore, LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion models. Notably, the low toxicity, hemolytic activity, and bleeding risk of LE6, along with its synthetic simplicity, underscore its clinical applicability. In conclusion, as an inhibitor of FXIIa and PK, LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mandarin fish von Hippel-Lindau protein regulates the NF-κB signaling pathway via interaction with IκB to promote fish ranavirus replication.","authors":"Zhi-Min Li, Xiao-Wei Qin, Qi Zhang, Jian He, Min-Cong Liang, Chuan-Rui Li, Yang Yu, Weng-Hui Liu, Shao-Ping Weng, Jian-Guo He, Chang-Jun Guo","doi":"10.24272/j.issn.2095-8137.2023.392","DOIUrl":"10.24272/j.issn.2095-8137.2023.392","url":null,"abstract":"<p><p>The von Hippel-Lindau tumor suppressor protein (VHL), an E3 ubiquitin ligase, functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors. Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway, although the specific molecular mechanisms remain unclear. Herein, the roles of mandarin fish ( <i>Siniperca chuatsi</i>) VHL ( <i>sc</i>VHL) in the NF-κB signaling pathway and mandarin fish ranavirus (MRV) replication were explored. The transcription of <i>sc</i>VHL was induced by immune stimulation and MRV infection, indicating a potential role in innate immunity. Dual-luciferase reporter gene assays and reverse transcription quantitative PCR (RT-qPCR) results demonstrated that <i>sc</i>VHL evoked and positively regulated the NF-κB signaling pathway. Treatment with NF-κB signaling pathway inhibitors indicated that the role of <i>sc</i>VHL may be mediated through <i>sc</i>IKKα, <i>sc</i>IKKβ, <i>sc</i>IκBα, or <i>sc</i>p65. Co-immunoprecipitation (Co-IP) analysis identified <i>sc</i>IκBα as a novel target protein of <i>sc</i>VHL. Moreover, <i>sc</i>VHL targeted <i>sc</i>IκBα to catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway. Following MRV infection, NF-κB signaling remained activated, which, in turn, promoted MRV replication. These findings suggest that <i>sc</i>VHL not only positively regulates NF-κB but also significantly enhances MRV replication. This study reveals a novel function of <i>sc</i>VHL in NF-κB signaling and viral infection in fish.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental models for preclinical research in kidney disease.","authors":"Jin Miao, Huanhuan Zhu, Junni Wang, Jianghua Chen, Fei Han, Weiqiang Lin","doi":"10.24272/j.issn.2095-8137.2024.072","DOIUrl":"10.24272/j.issn.2095-8137.2024.072","url":null,"abstract":"<p><p>Acute kidney injury (AKI) and chronic kidney disease (CKD) are significant public health issues associated with a long-term increase in mortality risk, resulting from various etiologies including renal ischemia, sepsis, drug toxicity, and diabetes mellitus. Numerous preclinical models have been developed to deepen our understanding of the pathophysiological mechanisms and therapeutic approaches for kidney diseases. Among these, rodent models have proven to be powerful tools in the discovery of novel therapeutics, while the development of kidney organoids has emerged as a promising advancement in the field. This review provides a comprehensive analysis of the construction methodologies, underlying biological mechanisms, and recent therapeutic developments across different AKI and CKD models. Additionally, this review summarizes the advantages, limitations, and challenges inherent in these preclinical models, thereby contributing robust evidence to support the development of effective therapeutic strategies.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effects of Pleistocene geological and climatic events on complex phylogeographic history of widespread sympatric species of Megaloptera in East Asia.","authors":"Ai-Li Lin, Ming-Ming Zou, Li-Jun Cao, Fumio Hayashi, Ding Yang, Xing-Yue Liu","doi":"10.24272/j.issn.2095-8137.2024.056","DOIUrl":"10.24272/j.issn.2095-8137.2024.056","url":null,"abstract":"<p><p>Unraveling the phylogeographic histories of species remains a key endeavor for comprehending the evolutionary processes contributing to the rich biodiversity and high endemism found in East Asia. In this study, we explored the phylogeographic patterns and demographic histories of three endemic fishfly and dobsonfly species ( <i>Neochauliodes formosanus</i>, <i>Protohermes costalis</i>, and <i>Neoneuromus orientalis</i>) belonging to the holometabolan order Megaloptera. These species, which share a broad and largely overlapping distribution, were analyzed using comprehensive mitogenomic data. Our findings revealed a consistent influence of vicariance on the population isolation of <i>Neoc. formosanus</i> and <i>P. costalis</i> between Hainan, Taiwan, and the East Asian mainland during the early Pleistocene, potentially hindering subsequent colonization of the later diverged <i>Neon. orientalis</i> to these islands. Additionally, we unveiled the dual function of the major mountain ranges in East Asia, serving both as barriers and conduits, in shaping the population structure of all three species. Notably, we demonstrated that these co-distributed species originated from Southwest, Southern, and eastern Central China, respectively, then subsequently migrated along multi-directional routes, leading to their sympatric distribution on the East Asian mainland. Furthermore, our results highlighted the significance of Pleistocene land bridges along the eastern coast of East Asia in facilitating the dispersal of mountain-dwelling insects with low dispersal ability. Overall, this study provides novel insight into the synergistic impact of Pleistocene geological and climatic events in shaping the diversity and distribution of aquatic insects in East Asia.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cadherin-18 loss in prospermatogonia and spermatogonial stem cells enhances cell adhesion through a compensatory mechanism.","authors":"Xiao-Xiao Li, Dan-Chen Zhang, Yan Wang, Jian Wen, Xing-Ju Wang, Yu-Lu Cao, Ru Jiang, Jia-Rui Li, Yi-Nuo Li, He-He Liu, Wen-Hai Xie, Zheng-Feng Xu, Ping Hu, Kang Zou","doi":"10.24272/j.issn.2095-8137.2023.373","DOIUrl":"10.24272/j.issn.2095-8137.2023.373","url":null,"abstract":"<p><p>Extracellular membrane proteins are crucial for mediating cell attachment, recognition, and signal transduction in the testicular microenvironment, particularly germline stem cells. Cadherin 18 (CDH18), a type II classical cadherin, is primarily expressed in the nervous and reproductive systems. Here, we investigated the expression of CDH18 in neonatal porcine prospermatogonia (ProSGs) and murine spermatogonial stem cells (SSCs). Disruption of CDH18 expression did not adversely affect cell morphology, proliferation, self-renewal, or differentiation in cultured porcine ProSGs, but enhanced cell adhesion and prolonged cell maintenance. Transcriptomic analysis indicated that the down-regulation of <i>CDH18</i> in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion. To further elucidate the function of CDH18 in germ cells, <i>Cdh18</i> knockout mice were generated, which exhibited normal testicular morphology, histology, and spermatogenesis. Transcriptomic analysis showed increased expression of genes associated with adhesion, consistent with the observations in porcine ProSGs. The interaction of CDH18 with β-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency. Collectively, these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs. Understanding this regulatory mechanism provides significant insights into the testicular niche.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCDC181 is required for sperm flagellum biogenesis and male fertility in mice.","authors":"Xiang-Jun Zhang, Xiao-Ning Hou, Jian-Teng Zhou, Bao-Lu Shi, Jing-Wei Ye, Meng-Lei Yang, Xiao-Hua Jiang, Bo Xu, Li-Min Wu, Qing-Hua Shi","doi":"10.24272/j.issn.2095-8137.2024.075","DOIUrl":"10.24272/j.issn.2095-8137.2024.075","url":null,"abstract":"<p><p>The structural integrity of the sperm flagellum is essential for proper sperm function. Flagellar defects can result in male infertility, yet the precise mechanisms underlying this relationship are not fully understood. CCDC181, a coiled-coil domain-containing protein, is known to localize on sperm flagella and at the basal regions of motile cilia. Despite this knowledge, the specific functions of CCDC181 in flagellum biogenesis remain unclear. In this study, <i>Ccdc181</i> knockout mice were generated. The absence of CCDC181 led to defective sperm head shaping and flagellum formation. Furthermore, the <i>Ccdc181</i> knockout mice exhibited extremely low sperm counts, grossly aberrant sperm morphologies, markedly diminished sperm motility, and typical multiple morphological abnormalities of the flagella (MMAF). Additionally, an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified, with CCDC181 regulating the localization of LRRC46 within sperm flagella. These findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosome-level genome and population genomics of the intermediate horseshoe bat ( <i>Rhinolophus affinis)</i> reveal the molecular basis of virus tolerance in <i>Rhinolophus</i> and echolocation call frequency variation.","authors":"Le Zhao, Jiaqing Yuan, Guiqiang Wang, Haohao Jing, Chen Huang, Lulu Xu, Xiao Xu, Ting Sun, Wu Chen, Xiuguang Mao, Gang Li","doi":"10.24272/j.issn.2095-8137.2024.027","DOIUrl":"10.24272/j.issn.2095-8137.2024.027","url":null,"abstract":"<p><p>Horseshoe bats (genus <i>Rhinolophus</i>, family Rhinolophidae) represent an important group within chiropteran phylogeny due to their distinctive traits, including constant high-frequency echolocation, rapid karyotype evolution, and unique immune system. Advances in evolutionary biology, supported by high-quality reference genomes and comprehensive whole-genome data, have significantly enhanced our understanding of species origins, speciation mechanisms, adaptive evolutionary processes, and phenotypic diversity. However, genomic research and understanding of the evolutionary patterns of <i>Rhinolophus</i> are severely constrained by limited data, with only a single published genome of <i>R. ferrumequinum</i> currently available. In this study, we constructed a high-quality chromosome-level reference genome for the intermediate horseshoe bat ( <i>R. affinis</i>). Comparative genomic analyses revealed potential genetic characteristics associated with virus tolerance in Rhinolophidae. Notably, we observed expansions in several immune-related gene families and identified various genes functionally associated with the SARS-CoV-2 signaling pathway, DNA repair, and apoptosis, which displayed signs of rapid evolution. In addition, we observed an expansion of the major histocompatibility complex class II (MHC-II) region and a higher copy number of the <i>HLA</i>- <i>DQB2</i> gene in horseshoe bats compared to other chiropteran species. Based on whole-genome resequencing and population genomic analyses, we identified multiple candidate loci (e.g., <i>GLI3</i>) associated with variations in echolocation call frequency across <i>R. affinis</i> subspecies. This research not only expands our understanding of the genetic characteristics of the <i>Rhinolophus</i> genus but also establishes a valuable foundation for future research.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic-based analysis reveals bile acid-mediated ovarian failure induced by low temperature in zebrafish.","authors":"Wen-Hao Li, Zhi-Qiang Li, Meng-Di Bu, Jia-Zhen Li, Liang-Biao Chen","doi":"10.24272/j.issn.2095-8137.2023.369","DOIUrl":"10.24272/j.issn.2095-8137.2023.369","url":null,"abstract":"<p><p>As ectotherms, fish are highly sensitive to temperature fluctuations, which can profoundly impact their reproductive cycles. In this study, we investigated the fertility and histological characteristics of zebrafish ( <i>Danio rerio</i>) ovaries exposed to a temperature gradient ranging from the thermopreferendum temperature of the species, 27°C, to lower temperatures of 22°C, 20°C, and 13°C over a period of two weeks. Comparative metabolomic (six biological replicates for each temperature) and transcriptomic (four biological replicates for each temperature) analyses were conducted under the four temperature conditions. Results indicated that lower temperatures inhibited oocyte development and differential metabolites were involved in steroid hormone production, antioxidant function, and lipid and protein catabolism. Disrupted reproductive hormones, increased proteolysis, and lipid degradation significantly impeded oocyte development and egg maturation. Notably, a significant increase in bile acid content was noted in the ovaries of the cold-treated fish, indicating that bile acids play a critical role in ovarian failure. Overall, these findings provide valuable insights into the mechanisms governing the reproductive response of fish to cold stress.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation.","authors":"Na Zhao, Xiu Chen, Qiu-Gu Chen, Xue-Ting Liu, Fan Geng, Meng-Meng Zhu, Fu-Ling Yan, Zhi-Jun Zhang, Qing-Guo Ren","doi":"10.24272/j.issn.2095-8137.2024.085","DOIUrl":"10.24272/j.issn.2095-8137.2024.085","url":null,"abstract":"<p><p>Emerging evidence indicates that sleep deprivation (SD) can lead to Alzheimer's disease (AD)-related pathological changes and cognitive decline. However, the underlying mechanisms remain obscure. In the present study, we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD. Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis, elevated NLRP3 inflammasome expression, GSK-3β activation, autophagy dysfunction, and tau hyperphosphorylation in the hippocampus. Colonization with the \"SD microbiota\" replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice. Remarkably, both the deletion of NLRP3 in <i>NLRP3</i> ^<i>-/-</i> mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux, suppressed tau hyperphosphorylation, and ameliorated cognitive deficits induced by chronic SD, while GSK-3β activity was not regulated by the NLRP3 inflammasome in chronic SD. Notably, deletion of NLRP3 reversed NLRP3 inflammasome activation, autophagy deficits, and tau hyperphosphorylation induced by GSK-3β activation in primary hippocampal neurons, suggesting that GSK-3β, as a regulator of NLRP3-mediated autophagy dysfunction, plays a significant role in promoting tau hyperphosphorylation. Thus, gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction, ultimately leading to cognitive deficits. Overall, these findings highlight GSK-3β as a regulator of NLRP3-mediated autophagy dysfunction, playing a critical role in promoting tau hyperphosphorylation.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance.","authors":"Yi-Fu Zhu, Rong-Hua Yu, Shuai Zhou, Pei-Pei Tang, Rui Zhang, Yu-Xin Wu, Ran Xu, Jia-Ming Wei, Ying-Ying Wang, Jia-Li Zhang, Meng-Ke Li, Xiao-Jing Shi, Yu-Wei Zhang, Guang-Zhi Liu, Rick F Thorne, Xu Dong Zhang, Mian Wu, Song Chen","doi":"10.24272/j.issn.2095-8137.2024.021","DOIUrl":"10.24272/j.issn.2095-8137.2024.021","url":null,"abstract":"<p><p>Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of <i>Fip200</i> severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as <i>Atg5</i>, <i>Atg16l1</i>, and <i>Atg7</i>, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of <i>Tax1bp1</i> in <i>fip200</i> ^<i>hGFAP</i> conditional knock-in (cKI) mice led to NSC deficiency, resembling the <i>fip200</i> ^<i>hGFAP</i> conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from <i>tax1bp1</i>-knockout <i>fip200</i> ^<i>hGFAP</i> cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of <i>Tax1bp1</i> in <i>fip200</i> ^<i>hGFAP</i> cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to <i>fip200</i> ^<i>hGFAP</i> cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}