Inhibition of amyloid formation of amyloid ß (1-42), amylin and insulin by 1,5-diazacyclooctanes, a spermine-acrolein conjugate.

Amyloid aggregates of proteins are known to be involved in various diseases such as Alzheimer's disease (AD). It is therefore speculated that the inhibition of amyloid formation can play an important role in the prevention of various diseases involving amyloids. Recently, we have found that acrolein reacts with polyamines, such as spermine, and produces 1,5-diazacyclooctane, such as cyclic spermine (cSPM). cSPM could suppress the aggregation of amyloid ß 1-40 (Aß40), one of the causative proteins of AD. This result suggests the potential inhibitory effect of cSPM against Aß 1-42 (Aß42) and other amyloid protein aggregation which are the main pathological features of AD and other diseases. However, the effect on the aggregation of such proteins remains unclear. In this study, the effect of cSPM on the amyloid formation of Aß42, amylin, and insulin was investigated. These three amyloidogenic proteins forming amyloids under physiological conditions (pH 7.4 and 37℃) served as model and are thought to be the causative proteins of AD, type 2 diabetes, and insulin-derived amyloidosis, respectively. Our results indicate that cSPM can suppress the amyloid aggregation of these proteins and reduce cytotoxicity. This study contributes to a better understanding of means to potentially counteract diseases by the means of polyamine and acrolein.

Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates.

Insulin balls, localized insulin amyloids formed at subcutaneous insulin-injection sites in patients with diabetes, cause poor glycemic control owing to impairments in insulin absorption. Our previous study has shown that some insulin balls are cytotoxic, but others are not, implying amyloid polymorphism. Interestingly, the patient with toxic insulin balls had been treated with antibiotic minocycline, suggesting a possible relationship between toxicity of insulin balls and minocycline. However, the direct effect of minocycline on the structure and cytotoxicity of the insulin amyloid is still unclear. Herein, we demonstrated that that minocycline at physiological concentrations induced degradation of insulin amyloids formed from human insulin and insulin drug preparations used for diabetes patients. Interestingly, the process involved the initial appearance of the toxic species, which subsequently changed into less-toxic species. It is also shown that the structure of the toxic species was similar to that of sonicated fragments of human insulin amyloids. Our study shed new light on the clarification of the revelation of insulin balls and the development of the insulin analogs for diabetes therapy.

YestroSens, a field-portable S. cerevisiae biosensor device for the detection of endocrine-disrupting chemicals: Reliability and stability.

Farming, industry and urbanization lead to increases in the concentrations of potentially harmful compounds in waste, surface and drinking waters. One example of such pollution are estrogens, the steroidal female reproductive hormones. Already at a few nanograms per litre, these hormones can trigger endocrine disruption and cause acute and chronic health problems in humans and wildlife. Here, we present a Saccharomyces cerevisiae estrogen biosensor capable of detecting estradiol, as well as ethinylestradiol, at concentrations of 1 nM. After an initial characterization of the sensor strain performance in an optimal laboratory setting, we focused on developing a biosensor device. We addressed current limitations of biosensors, such as the requirement of the cells for a liquid growth matrix, controlled storage conditions required to preserve cell viability, and the usually required bulky, as well as expensive, laboratory equipment. Our study provides significant new insights into the field of applied biosensors. The system presented in this work takes microorganism-based analytics one step closer to field application in decentralized locations.