INTRODUCTION Ghrelin is a 28-amino-acid peptide hormone initially identified in the rat stomach that acts as an endogenous ligand for the growth hormone secretagogue receptor 1. Ghrelin circulates in the blood as two main isoforms: octanoylated ghrelin and des-acyl ghrelin 2. Octanoylated ghrelin, the active form, stimulates appetite and induces body weight gain, whereas des-acyl ghrelin, which has no acyl modification, does not have these activities 3. Furthermore, octanoylated ghrelin decreases energy expenditure by decreasing oxygen consumption and suppressing thermogenesis in brown adipose tissue 4 6. Therefore, lowering plasma octanoylated ghrelin levels may be an important strategy for the prevention and treatment of obesity. The conversion of the proghrelin precursor to octanoylated ghrelin involves two steps, i.e., octanoylation at the serine-3 residue, which is catalyzed by ghrelin O-acyl transferase GOAT 7 9 , and cleavage by prohormone convertases PC , such as furin, PC1/3, or PC2 10, 11. In ghrelin octanoylation, octanoyl-CoA is a substrate for GOAT. Oc
Defining the morphological disorders causing neurodegenerative diseases is an unresolved problem. In this study, we propose a statistical−physical approach to quantify neurite morphology and evaluate the pathological states induced by Alzheimer's disease (AD). We analyzed the two-dimensional morphologies of neurites of in vitro-cultured human induced-pluripotent stem cell-derived neurons, reprogrammed from both a healthy person and a patient with AD, using discrete chordal Loewner evolution. For the numerically calculated Loewner driving forces, detrended fluctuation analysis was performed, and the morphological characteristics of the neurites were quantified using short-range and long-range scaling exponents. The day in vitro (DIV)-dependent behaviors of the scaling exponents and the associated neurite-type categorizations suggested that differences between healthy and AD neurites can be observed from the early stage (DIV3) of their development. Notably, AD neurites have less long-range autocorrelations than healthy neurites, particularly in the earlier stages (DIV3–10). Immunofluorescence-staining results suggested that these differences precede significant expressions of β-amyloid and phosphorylated tau, which are known as biological factors causing AD. We expect that these results will lead to a theoretical interpretation of the neurogenerative disease, providing the physical properties of individual neurites with different morphologies.
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