Urolithin A suppresses high glucose-induced neuronal amyloidogenesis by modulating TGM2-dependent ER-mitochondria contacts and calcium homeostasis.

1. Cell Death Differ. 2021 Jan;28(1):184-202. doi: 10.1038/s41418-020-0593-1. Epub 2020 Jul 23. Urolithin A suppresses high glucose-induced neuronal amyloidogenesis by modulating TGM2-dependent ER-mitochondria contacts and calcium homeostasis. Lee HJ(#)(1)(2), Jung YH(#)(3), Choi GE(3), Kim JS(3), Chae CW(3), Lim JR(3), Kim SY(3), Yoon JH(3), Cho JH(3), Lee SJ(4), Han HJ(5). Author information: (1)Laboratory of Veterinary Physiology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, South Korea. (2)Institute for Stem Cell and Regenerative Medicine (ISCRM), Chungbuk National University, Cheongju, Chungbuk, 28644, South Korea. (3)Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science Research, Seoul National University, Seoul, 08826, South Korea. (4)Department of Pharmaceutical Engineering, Daegu Haany University, Gyeongsan, 38610, South Korea. (5)Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science Research, Seoul National University, Seoul, 08826, South Korea. hjhan@snu.ac.kr. (#)Contributed equally Hyperglycemia in diabetes mellitus (DM) patients is a causative factor for amyloidogenesis and induces neuropathological changes, such as impaired neuronal integrity, neurodegeneration, and cognitive impairment. Regulation of mitochondrial calcium influx from the endoplasmic reticulum (ER) is considered a promising strategy for the prevention of mitochondrial ROS (mtROS) accumulation that occurs in the Alzheimer's disease (AD)-associated pathogenesis in DM patients. Among the metabolites of ellagitannins that are produced in the gut microbiome, urolithin A has received an increasing amount of attention as a novel candidate with anti-oxidative and neuroprotective effects in AD. Here, we inv