Hyperglycemic Neurovasculature‐On‐A‐Chip to Study the Effect of SIRT1‐Targeted Therapy for the Type 3 Diabetes “Alzheimer's Disease”

Minjeong Jang; Nakwon Choi; Hong Nam Kim

doi:10.1002/advs.202201882

journal article Open Access Sep 08, 2022

Hyperglycemic Neurovasculature‐On‐A‐Chip to Study the Effect of SIRT1‐Targeted Therapy for the Type 3 Diabetes “Alzheimer's Disease”

Minjeong Jang Nakwon Choi

Hong Nam Kim

Advanced Science Vol. 9 No. 34 · Wiley

View at Publisher Save 10.1002/advs.202201882

Abstract

AbstractDiabetes 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.

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References

Details

Published: Sep 08, 2022
Vol/Issue: 9(34)
License: View

Authors

M

Minjeong Jang

Brain Science Institute Korea Institute of Science and Technology (KIST) Seoul 02792 Republic of Korea

N

Nakwon Choi

Brain Science Institute Korea Institute of Science and Technology (KIST) Seoul 02792 Republic of Korea; Division of Bio‐Medical Science & Technology KIST School Republic of Korea University of Science and Technology Seoul 02792 Republic of Korea; KU‐KIST Graduate School of Converging Science and Technology Korea University Seoul 02841 Republic of Korea

H

Hong Nam Kim

Brain Science Institute Korea Institute of Science and Technology (KIST) Seoul 02792 Republic of Korea; Division of Bio‐Medical Science & Technology KIST School Republic of Korea University of Science and Technology Seoul 02792 Republic of Korea; School of Mechanical Engineering Yonsei University Seoul 03722 Republic of Korea; Yonsei‐KIST Convergence Research Institute Yonsei University Seoul 03722 Republic of Korea

Funding

National Research Foundation of Korea Award: 2021R1A2B5B02086828

Cite This Article

Minjeong Jang, Nakwon Choi, Hong Nam Kim (2022). Hyperglycemic Neurovasculature‐On‐A‐Chip to Study the Effect of SIRT1‐Targeted Therapy for the Type 3 Diabetes “Alzheimer's Disease”. Advanced Science, 9(34). https://doi.org/10.1002/advs.202201882

Hyperglycemic Neurovasculature‐On‐A‐Chip to Study the Effect of SIRT1‐Targeted Therapy for the Type 3 Diabetes “Alzheimer's Disease”

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