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Hyperglycemic Neurovasculature‐On‐A‐Chip to Study the Effect of SIRT1‐Targeted Therapy for the Type 3 Diabetes “Alzheimer's Disease”
Diabetes mellitus (DM) is closely related to Alzheimer's disease (AD), but individual cellular changes and the possibilities of recovery through molecular level regulation have not been investigated. Here, a neurovasculature‐on‐a‐chip (NV chip) model is presented in which the perfusable brain m...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9731710/ https://www.ncbi.nlm.nih.gov/pubmed/36073820 http://dx.doi.org/10.1002/advs.202201882 |
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author | Jang, Minjeong Choi, Nakwon Kim, Hong Nam |
author_facet | Jang, Minjeong Choi, Nakwon Kim, Hong Nam |
author_sort | Jang, Minjeong |
collection | PubMed |
description | Diabetes mellitus (DM) is closely related to Alzheimer's disease (AD), but individual cellular changes and the possibilities of recovery through molecular level regulation have not been investigated. Here, a neurovasculature‐on‐a‐chip (NV chip) model is presented in which the perfusable brain microvasculature is surrounded by the neurons. Under hyperglycemic conditions, the brain microvasculature shows disruption of barrier function and reduced expression of junctional markers. The neurons show Tau pathology and amyloid‐beta (Aß) accumulation. Endothelial cells and neurons in the NV chip show sirtuin 1 (SIRT1) downregulation under hyperglycemic conditions, suggesting SIRT1 as a key regulator of hyperglycemia‐induced AD. The recovery of glucose levels rescue SIRT1 expression, suggesting that this type of intervention may rescue the progression of hyperglycemia‐mediated AD. Furthermore, the short hairpin RNA (shRNA)‐, clustered regularly interspaced short palindromic repeats (CRISPR)‐, and pharmaceutics‐mediated regulation of SIRT1 regulate the pathophysiology of the brain endothelium and neurons at the functional and molecular levels. |
format | Online Article Text |
id | pubmed-9731710 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97317102022-12-12 Hyperglycemic Neurovasculature‐On‐A‐Chip to Study the Effect of SIRT1‐Targeted Therapy for the Type 3 Diabetes “Alzheimer's Disease” Jang, Minjeong Choi, Nakwon Kim, Hong Nam Adv Sci (Weinh) Research Articles Diabetes mellitus (DM) is closely related to Alzheimer's disease (AD), but individual cellular changes and the possibilities of recovery through molecular level regulation have not been investigated. Here, a neurovasculature‐on‐a‐chip (NV chip) model is presented in which the perfusable brain microvasculature is surrounded by the neurons. Under hyperglycemic conditions, the brain microvasculature shows disruption of barrier function and reduced expression of junctional markers. The neurons show Tau pathology and amyloid‐beta (Aß) accumulation. Endothelial cells and neurons in the NV chip show sirtuin 1 (SIRT1) downregulation under hyperglycemic conditions, suggesting SIRT1 as a key regulator of hyperglycemia‐induced AD. The recovery of glucose levels rescue SIRT1 expression, suggesting that this type of intervention may rescue the progression of hyperglycemia‐mediated AD. Furthermore, the short hairpin RNA (shRNA)‐, clustered regularly interspaced short palindromic repeats (CRISPR)‐, and pharmaceutics‐mediated regulation of SIRT1 regulate the pathophysiology of the brain endothelium and neurons at the functional and molecular levels. John Wiley and Sons Inc. 2022-09-08 /pmc/articles/PMC9731710/ /pubmed/36073820 http://dx.doi.org/10.1002/advs.202201882 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Jang, Minjeong Choi, Nakwon Kim, Hong Nam Hyperglycemic Neurovasculature‐On‐A‐Chip to Study the Effect of SIRT1‐Targeted Therapy for the Type 3 Diabetes “Alzheimer's Disease” |
title | Hyperglycemic Neurovasculature‐On‐A‐Chip to Study the Effect of SIRT1‐Targeted Therapy for the Type 3 Diabetes “Alzheimer's Disease” |
title_full | Hyperglycemic Neurovasculature‐On‐A‐Chip to Study the Effect of SIRT1‐Targeted Therapy for the Type 3 Diabetes “Alzheimer's Disease” |
title_fullStr | Hyperglycemic Neurovasculature‐On‐A‐Chip to Study the Effect of SIRT1‐Targeted Therapy for the Type 3 Diabetes “Alzheimer's Disease” |
title_full_unstemmed | Hyperglycemic Neurovasculature‐On‐A‐Chip to Study the Effect of SIRT1‐Targeted Therapy for the Type 3 Diabetes “Alzheimer's Disease” |
title_short | Hyperglycemic Neurovasculature‐On‐A‐Chip to Study the Effect of SIRT1‐Targeted Therapy for the Type 3 Diabetes “Alzheimer's Disease” |
title_sort | hyperglycemic neurovasculature‐on‐a‐chip to study the effect of sirt1‐targeted therapy for the type 3 diabetes “alzheimer's disease” |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9731710/ https://www.ncbi.nlm.nih.gov/pubmed/36073820 http://dx.doi.org/10.1002/advs.202201882 |
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