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WFRF:(Li Xing Yu)
 

Sökning: WFRF:(Li Xing Yu) > AβPP-tau-HAS1 axis ...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003904naa a2200481 4500
001oai:lup.lub.lu.se:f7ad97f1-7531-4690-b9c9-709ad391f393
003SwePub
008240424s2024 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/f7ad97f1-7531-4690-b9c9-709ad391f3932 URI
0247 a https://doi.org/10.1016/j.matbio.2024.03.0032 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Zhang, Ya Hongu Northeastern University4 aut
2451 0a AβPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease
264 1c 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 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650 7a 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
7001 a Sun, Xing Tongu Northeastern University4 aut
7001 a Guo, Rui Fangu Northeastern University4 aut
7001 a Feng, Gang Yiu Northeastern University4 aut
7001 a Gao, Hui Lingu Northeastern University4 aut
7001 a Zhong, Man Liu Northeastern University4 aut
7001 a Tian, Li Wenu Northeastern University4 aut
7001 a Qiu, Zhong Yiu Northeastern University4 aut
7001 a Cui, Yu Weiu Northeastern University4 aut
7001 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
7001 a Zhao, Puu Northeastern University4 aut
7102 a Northeastern Universityb Neural plasticitet och reparation4 org
7730 t Matrix Biologyg 129, s. 29-43q 129<29-43x 0945-053X
8564 u http://dx.doi.org/10.1016/j.matbio.2024.03.003y FULLTEXT
8564 8u https://lup.lub.lu.se/record/f7ad97f1-7531-4690-b9c9-709ad391f393
8564 8u https://doi.org/10.1016/j.matbio.2024.03.003

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