Ribosylation-Derived Advanced Glycation End Products Induce Tau Hyperphosphorylation Through Brain-Derived Neurotrophic Factor Reduction
Advanced glycation end products (AGEs) have been implicated in the disease process of diabetes mellitus. They have also been found in senile plaques and neurofibrillary tangles in the brains of Alzheimer's disease patients. Furthermore, abnormally high levels of D-ribose and D-glucose were found in the urine of patients with type 2 diabetes mellitus, suggesting that diabetic patients suffer from dysmetabolism of not only D-glucose but also D-ribose. In the present study, intravenous tail injections of ribosylated rat serum albumin (RRSA) were found to impair memory in rats, but they did not markedly impair learning, as measured by the Morris water maze test. Injections of RRSA were found to trigger tau hyperphosphorylation in the rat hippocampus via GSK-3β activation. Tau hyperphosphorylation and GSK-3β activation were also observed in N2a cells in the presence of ribosylation-derived AGEs. Furthermore, the administration of ribosylation-derived AGEs induced the suppression of brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB). Both GSK-3β inhibition and BDNF treatment decreased the levels of phosphorylated tau in N2a cells. In particular, the administration of BDNF could rescue memory failure in ribosylated AGE-injected rats. Ribosylation-derived AGEs downregulated the BDNF-TrkB pathway in rat brains and N2a cells, leading to GSK-3β activation-mediated tau hyperphosphorylation, which was involved in the observed rat memory loss. Targeting ribosylation may be a promising therapeutic strategy to prevent Alzheimer's disease and diabetic encephalopathies.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:71 |
|---|---|
| Enthalten in: |
Journal of Alzheimer's disease : JAD - 71(2019), 1 vom: 26., Seite 291-305 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wu, Beibei [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 13.10.2020 Date Revised 13.10.2020 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.3233/JAD-190158 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM299925552 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM299925552 | ||
| 003 | DE-627 | ||
| 005 | 20231225101413.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3233/JAD-190158 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0999.xml |
| 035 | |a (DE-627)NLM299925552 | ||
| 035 | |a (NLM)31381511 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wu, Beibei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ribosylation-Derived Advanced Glycation End Products Induce Tau Hyperphosphorylation Through Brain-Derived Neurotrophic Factor Reduction |
| 264 | 1 | |c 2019 | |
| 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 Completed 13.10.2020 | ||
| 500 | |a Date Revised 13.10.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Advanced glycation end products (AGEs) have been implicated in the disease process of diabetes mellitus. They have also been found in senile plaques and neurofibrillary tangles in the brains of Alzheimer's disease patients. Furthermore, abnormally high levels of D-ribose and D-glucose were found in the urine of patients with type 2 diabetes mellitus, suggesting that diabetic patients suffer from dysmetabolism of not only D-glucose but also D-ribose. In the present study, intravenous tail injections of ribosylated rat serum albumin (RRSA) were found to impair memory in rats, but they did not markedly impair learning, as measured by the Morris water maze test. Injections of RRSA were found to trigger tau hyperphosphorylation in the rat hippocampus via GSK-3β activation. Tau hyperphosphorylation and GSK-3β activation were also observed in N2a cells in the presence of ribosylation-derived AGEs. Furthermore, the administration of ribosylation-derived AGEs induced the suppression of brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB). Both GSK-3β inhibition and BDNF treatment decreased the levels of phosphorylated tau in N2a cells. In particular, the administration of BDNF could rescue memory failure in ribosylated AGE-injected rats. Ribosylation-derived AGEs downregulated the BDNF-TrkB pathway in rat brains and N2a cells, leading to GSK-3β activation-mediated tau hyperphosphorylation, which was involved in the observed rat memory loss. Targeting ribosylation may be a promising therapeutic strategy to prevent Alzheimer's disease and diabetic encephalopathies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Advanced glycation end products | |
| 650 | 4 | |a GSK-3β oxidative stress | |
| 650 | 4 | |a brain-derived neurotrophic factor | |
| 650 | 4 | |a ribosylation | |
| 650 | 4 | |a tau hyperphosphorylation | |
| 650 | 7 | |a Glycation End Products, Advanced |2 NLM | |
| 650 | 7 | |a tau Proteins |2 NLM | |
| 650 | 7 | |a Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.- |2 NLM | |
| 650 | 7 | |a Glycogen Synthase Kinase 3 beta |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a tropomyosin kinase |2 NLM | |
| 650 | 7 | |a EC 2.7.11.28 |2 NLM | |
| 700 | 1 | |a Wang, Yujing |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Chenggang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yao |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Lexiang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Weiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a He, Rongqiao |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of Alzheimer's disease : JAD |d 1998 |g 71(2019), 1 vom: 26., Seite 291-305 |w (DE-627)NLM097527327 |x 1875-8908 |7 nnns |
| 773 | 1 | 8 | |g volume:71 |g year:2019 |g number:1 |g day:26 |g pages:291-305 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3233/JAD-190158 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 71 |j 2019 |e 1 |b 26 |h 291-305 | ||