Optogenetic and chemogenetic approaches for modeling neurological disorders in vivo.

Animal models of human neurological disorders provide valuable experimental tools which enable us to study various aspects of disorder pathogeneses, ranging from structural abnormalities and disrupted metabolism and signaling to motor and mental deficits, and allow us to test novel therapies in preclinical studies. To be valid, these animal models should recapitulate complex pathological features at the molecular, cellular, tissue, and behavioral levels as closely as possible to those observed in human subjects. Pathological states resembling known human neurological disorders can be induced in animal species by toxins, genetic factors, lesioning, or exposure to extreme conditions. In recent years, novel animal models recapitulating neuropathologies in humans have been introduced. These animal models are based on synthetic biology approaches: opto- and chemogenetics. In this paper, we review recent opto- and chemogenetics-based animal models of human neurological disorders. These models allow for the creation of pathological states by disrupting specific processes at the cellular level. The artificial pathological states mimic a range of human neurological disorders, such as aging-related dementia, Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, epilepsy, and ataxias. Opto- and chemogenetics provide new opportunities unavailable with other animal models of human neurological disorders. These techniques enable researchers to induce neuropathological states varying in severity and ranging from acute to chronic. We also discuss future directions for the development and application of synthetic biology approaches for modeling neurological disorders.

Hydrogen peroxide is not generated intracellularly in human neural spheroids during ischemia-reperfusion.

Reactive oxygen species (ROS) are considered a primary source of damage during ischemic stroke. However, the precise timing of ROS production (during hypoxia or reperfusion) remains unclear. Cellular 3D spheroids are often proposed as an optimal alternative to both 2D cell cultures and animal models in modeling disease conditions. Here we report live imaging of hydrogen peroxide dynamics during the acute phase of hypoxia and reperfusion in human iPSC-derived neural spheroids, stably expressing fluorescent biosensor HyPer7. Contrary to previous reports, we did not observe a hydrogen peroxide production burst neither during hypoxia nor in course of reperfusion. Our data suggest either lack of oxidative stress during ischemia-reperfusion in spheroids or existence of different mechanisms of oxidative damage.

Will Peptides Help to Stop COVID-19?

Peptides are widely used for the diagnostics, prevention, and therapy of certain human diseases. How useful can they be for the disease caused by the SARS-CoV-2 coronavirus? In this review, we discuss the possibility of using synthetic and recombinant peptides and polypeptides for prevention of COVID-19 via blocking the interaction between the virus and its main receptor ACE2, as well as components of antiviral vaccines, in particular, against new emerging virus variants.