Sökning: onr:"swepub:oai:lup.lub.lu.se:f7ad97f1-7531-4690-b9c9-709ad391f393" > AβPP-tau-HAS1 axis ...
Fältnamn | Indikatorer | Metadata |
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000 | 03904naa a2200481 4500 | |
001 | oai:lup.lub.lu.se:f7ad97f1-7531-4690-b9c9-709ad391f393 | |
003 | SwePub | |
008 | 240424s2024 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/f7ad97f1-7531-4690-b9c9-709ad391f3932 URI |
024 | 7 | a https://doi.org/10.1016/j.matbio.2024.03.0032 DOI |
040 | a (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Zhang, Ya Hongu Northeastern University4 aut |
245 | 1 0 | a AβPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease |
264 | 1 | c 2024 |
300 | a 15 s. | |
520 | a As the backbone of the extracellular matrix (ECM) and the perineuronal nets (PNNs), hyaluronic acid (HA) provides binding sites for proteoglycans and other ECM components. Although the pivotal of HA has been recognized in Alzheimer's disease (AD), few studies have addressed the relationship between AD pathology and HA synthases (HASs). Here, HASs in different regions of AD brains were screened in transcriptomic database and validated in AβPP/PS1 mice. We found that HAS1 was distributed along the axon and nucleus. Its transcripts were reduced in AD patients and AβPP/PS1 mice. Phosphorylated tau (p-tau) mediates AβPP-induced cytosolic-nuclear translocation of HAS1, and negatively regulated the stability, monoubiquitination, and oligomerization of HAS1, thus reduced the synthesis and release of HA. Furthermore, non-ubiquitinated HAS1 mutant lost its enzyme activity, and translocated from the cytosol into the nucleus, forming nuclear speckles (NS). Unlike the splicing-related NS, less than 1 % of the non-ubiquitinated HAS1 co-localized with SRRM2, proving the regulatory role of HAS1 in gene transcription, indirectly. Thus, differentially expressed genes (DEGs) related to both non-ubiquitinated HAS1 mutant and AD were screened using transcriptomic datasets. Thirty-nine DEGs were identified, with 64.1 % (25/39) showing consistent results in both datasets. Together, we unearthed an important function of the AβPP-p-tau-HAS1 axis in microenvironment remodeling and gene transcription during AD progression, involving the ubiquitin-proteasome, lysosome, and NS systems. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
653 | a Alzheimer's disease | |
653 | a Extracellular matrix | |
653 | a Hyaluronan synthases | |
653 | a Nuclear speckles | |
653 | a Phosphorylated tau | |
653 | a Ubiquitylation | |
700 | 1 | a Sun, Xing Tongu Northeastern University4 aut |
700 | 1 | a Guo, Rui Fangu Northeastern University4 aut |
700 | 1 | a Feng, Gang Yiu Northeastern University4 aut |
700 | 1 | a Gao, Hui Lingu Northeastern University4 aut |
700 | 1 | a Zhong, Man Liu Northeastern University4 aut |
700 | 1 | a Tian, Li Wenu Northeastern University4 aut |
700 | 1 | a Qiu, Zhong Yiu Northeastern University4 aut |
700 | 1 | a Cui, Yu Weiu Northeastern University4 aut |
700 | 1 | a Li, Jia Yiu Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,China Medical University, Shenyang4 aut0 (Swepub:lu)mphy-jli |
700 | 1 | a Zhao, Puu Northeastern University4 aut |
710 | 2 | a Northeastern Universityb Neural plasticitet och reparation4 org |
773 | 0 | t Matrix Biologyg 129, s. 29-43q 129<29-43x 0945-053X |
856 | 4 | u http://dx.doi.org/10.1016/j.matbio.2024.03.003y FULLTEXT |
856 | 4 8 | u https://lup.lub.lu.se/record/f7ad97f1-7531-4690-b9c9-709ad391f393 |
856 | 4 8 | u https://doi.org/10.1016/j.matbio.2024.03.003 |
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