Jang, Minjeong Choi, Nakwon Kim, Hong Nam 2024-01-19T10:33:42Z 2024-01-19T10:33:42Z 2022-09-22 2022-12 2198-3844 https://pubs.kist.re.kr/handle/201004/114267 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. English Wiley-VCH Verlag Hyperglycemic Neurovasculature-On-A-Chip to Study the Effect of SIRT1-Targeted Therapy for the Type 3 Diabetes "Alzheimer's Disease" Article 10.1002/advs.202201882 1 Advanced Science, v.9, no.34 Advanced Science 9 34 Y scie scopus 000850889700001 Chemistry, Multidisciplinary Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article SIRT1 MODEL NEURODEGENERATION DYSFUNCTION Alzheimer&apos s disease diabetes hyperglycemia neurovasculature-on-a-chip