AβPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease
Copyright © 2024. Published by Elsevier B.V..
As the backbone of the extracellular matrix (ECM) and the perineuronal nets, 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 databases 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Matrix biology : journal of the International Society for Matrix Biology - (2024) vom: 20. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhang, Ya-Hong [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Alzheimer's disease |
|---|
| Anmerkungen: |
Date Revised 22.03.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1016/j.matbio.2024.03.003 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370084888 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370084888 | ||
| 003 | DE-627 | ||
| 005 | 20240324000120.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240324s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.matbio.2024.03.003 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1343.xml |
| 035 | |a (DE-627)NLM370084888 | ||
| 035 | |a (NLM)38518923 | ||
| 035 | |a (PII)S0945-053X(24)00039-8 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhang, Ya-Hong |e verfasserin |4 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 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 22.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2024. Published by Elsevier B.V. | ||
| 520 | |a As the backbone of the extracellular matrix (ECM) and the perineuronal nets, 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 databases 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 | 4 | |a Journal Article | |
| 650 | 4 | |a Alzheimer's disease | |
| 650 | 4 | |a extracellular matrix | |
| 650 | 4 | |a hyaluronan synthases | |
| 650 | 4 | |a nuclear speckles | |
| 650 | 4 | |a phosphorylated tau | |
| 650 | 4 | |a ubiquitylation | |
| 700 | 1 | |a Sun, Xing-Tong |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Rui-Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Gang-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Hui-Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Man-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Li-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Zhong-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Yu-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jia-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Pu |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Matrix biology : journal of the International Society for Matrix Biology |d 1996 |g (2024) vom: 20. März |w (DE-627)NLM074964305 |x 1569-1802 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:20 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.matbio.2024.03.003 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 20 |c 03 | ||