한빛사 논문
Minjeong Jang, Nakwon Choi, and Hong Nam Kim*
M. Jang, N. Choi, H. N. Kim
Brain Science Institute Korea Institute of Science and Technology (KIST) Seoul 02792, Republic of Korea
N. Choi, H. N. Kim
Division of Bio-Medical Science & Technology KIST School Republic of Korea University of Science and Technology Seoul 02792, Republic of Korea
N. Choi
KU-KIST Graduate School of Converging Science and Technology Korea University Seoul 02841, Republic of Korea
H. N. Kim
School of Mechanical Engineering Yonsei University Seoul 03722, Republic of Korea
H. N. Kim
Yonsei-KIST Convergence Research Institute Yonsei University Seoul 03722, Republic of Korea
*Corresponding author.
Abstract
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.
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