Non-fibril form but not fibril form of human islet amyloid polypeptide 8–20 changes brain functions in mice

Abstract

Whether fibril formation increases or decreases cytotoxicity remains unclear. Aggregation of human islet amyloid polypeptide (hIAPP), a pivotal regulator of glucose homeostasis, impairs the function and viability of pancreatic β cells. Evidence suggests that low-order oligomers of hIAPP are more toxic to β cells than fibril. However, it remains unclear whether non-fibril form of hIAPP specifically alters brain functions. This study produced fibril and non-fibril forms from a single hIAPP 8–20 peptide. The non-fibril form-injected mice showed changes in spontaneous motor activities, preference for location in the open field and social behavior. In contrast, the fibril-injected mice showed no changes in these behavioral tests. In line with the behavioral changes, the non-fibril form led to impaired neurite outgrowth of cultured neuron-like cells and the loss of neurons in the mouse hippocampus. These findings suggest that non-fibril form but not fibril form of hIAPP changes brain functions.

Computational Investigation of Coaggregation and Cross-Seeding between Aβ and hIAPP Underpinning the Cross-Talk in Alzheimer’s Disease and Type 2 Diabetes

“…Residues 10–29 featured a greater average number of interpeptide hIAPP–hIAPP contacts than other regions, indicating that this region served as the hotspot driving the aggregation of hIAPP (Figure S6b). The independent formation of β-sheet-rich fibrillar structures for the segments of hIAPP 8–20 , , hIAPP 15–25 , , hIAPP 19–29 , , and hIAPP 22–29 , both in vitro and in silico , also suggested the propensity of these regions to contribute to the overall aggregation process.…”

Optimization of chaotic light output in semiconductor laser systems based on multi-objective optimization algorithm

“…x 3 ] T , and the total disturbance p is differentiable, the system vector is expressed as formula (5). T .…”

“…In addition, there are some problems with the spectral width and dynamic range of chaotic light output by semiconductor lasers, which directly affect signal transmission and data capacity. At present, the chaotic light output by SLS usually has problems of narrow spectral width and limited dynamic range, which limit the performance in high-speed data transmission and other applications [ 5 ]. In this context, a power control algorithm for semiconductor laser drive systems was studied, and a chaotic optical performance optimization model based on Multi-objective Genetic Algorithm (MOGA) was constructed.…”