旭硝子財団助成研究成果報告2023

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108Chanat AONBANGKHEN109Kanthida KUSONMANOA Novel Strategy for Studying and Treating Alzheimer’s Disease using Protein Dimerization(Project 2022)High-Resolution Study of Fecal Microbiome in Thai Captive Elephants Towards Nutrition Management and Welfare Improvement(Project 2021)旭硝子財団　助成研究成果報告（2023）Alzheimer’s Disease (AD) is the most common form of neurodegenerative disorder caused by abnormal intracellular and extracellular aggregation of specific proteins. Neurofibrillary Tangles (NFTs) are one of the common markers in the brain suffering from Alzheimer’s Disease which is primarily caused by the hyperphosphorylation of Tau proteins and subsequent aggregation. In this study, we will utilize a novel strategy called protein dimerization technique via translocation and degradation of the calpain enzyme to regulate the activity of CDK5 and reduce the subsequent effect of the hyperphosphorylation of tau protein. In parallel, in order to detect and visualize tau protein in vitro and in cells, we have been developing fluorescent sensors, which can bind to tau protein specifically. Thus, in this report, we will present the progress on the development of fluorescent compounds as a new tool to studying tau protein first. This study will be a very useful and a starting point forward into exploring the pathobiology of many neurodegenerative diseases at the molecular level. This novel strategy will facilitate the development of new and potent therapeutics for the treatment of Alzheimer’s Disease, which will benefit millions of people worldwide.Asian elephants (Elephas maximus) have been known as a national symbol of Thailand and linked to Thai history and culture for centuries. The elephant welfare improvement is one of the major components to achieve sustainable captive management. Microbiome inhabiting digestive tracts have been shown with symbiotic relation to host health helping in dietary digestion, stimulating immunes and protecting pathogens colonization. In this project, we provided a high-resolution study of microbiome of 32 Thai captive elephants at species level by utilizing full-length 16S rRNA gene nanopore sequencing. The majority of microbial phyla of Thai elephant gut microbiomes are Firmicutes, Bacteroidota, Verrucomicrobiota, and Proteobacteria. At the species level, seven common dominant microbial taxa were revealed, which are uncultured Rikenellaceae RC9 gut group, uncultured Kiritimatiellae WCHB1-41, uncultured Phascolarctobacterium, uncultured Oscillospiraceae NK4A214 group, uncultured Christensenellaceae R-7 group, uncultured Oribacterium, uncultured Oscillospirales UCG-010, and uncultured Lachnospiraceae. We observed microbiome shifts along the age classes of baby (0-2 years), juvenile (2-10 years), and adult (>10 years). In addition, significant differences between microbiome profiles have also been revealed in elephants fed with a diet type (including milk, banana, napier grass, native grass, and pineapple) and without. Interestingly, we found distinct microbiome profiles among adult elephants fed with local plants, Caryota urens as a supplement, and napier grass as a part of the main diet. Different beneficial microbes have been revealed according to age classes and feed diets. The retrieved microbiome data could be provided as good baseline microbial profiles for monitoring elephant health, and a guideline for feeding selection towards age classes and diets.78