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AβPP-tau-HAS1 axis ...
AβPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease
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- Zhang, Ya Hong (författare)
- Northeastern University
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- Sun, Xing Tong (författare)
- Northeastern University
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- Guo, Rui Fang (författare)
- Northeastern University
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- Feng, Gang Yi (författare)
- Northeastern University
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- Gao, Hui Ling (författare)
- Northeastern University
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- Zhong, Man Li (författare)
- Northeastern University
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- Tian, Li Wen (författare)
- Northeastern University
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- Qiu, Zhong Yi (författare)
- Northeastern University
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- Cui, Yu Wei (författare)
- Northeastern University
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- Li, Jia Yi (författare)
- Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,China Medical University, Shenyang
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- Zhao, Pu (författare)
- Northeastern University
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(creator_code:org_t)
- 2024
- 2024
- Engelska 15 s.
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Ingår i: Matrix Biology. - 0945-053X. ; 129, s. 29-43
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- Alzheimer's disease
- Extracellular matrix
- Hyaluronan synthases
- Nuclear speckles
- Phosphorylated tau
- Ubiquitylation
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Zhang, Ya Hong
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Sun, Xing Tong
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Guo, Rui Fang
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Feng, Gang Yi
-
Gao, Hui Ling
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Zhong, Man Li
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visa fler...
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Tian, Li Wen
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Qiu, Zhong Yi
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Cui, Yu Wei
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Li, Jia Yi
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Zhao, Pu
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Medicinsk geneti ...
- Artiklar i publikationen
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Matrix Biology
- Av lärosätet
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Lunds universitet