Exosomes are extracellular vesicles that represent an important mode of intercellular communication. It is thought that exosomes can carry biologically active molecules associated with the progressive spreading of amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disease characterized by the progressive death of motor neurons. Angiogenin is likely to be important in the pathogenesis of ALS. This paper analyzes the content of angiogenin in blood plasma, CSF, and exosome fractions obtained from blood plasma and CSF in ALS. The study included 30 patients with ALS and 26 age and gender matched healthy controls. The relative amount of angiogenin in plasma and CSF was significantly higher than in exosome fractions (p< 0.05). A comparison of angiogenin content in plasma and exosome fraction revealed lower angiogenin levels in patients with ALS compared to healthy volunteers (p< 0.05), which may indicate a protective role of angiogenin. Higher concentrations of angiogenin in plasma and its exosome fractions tended to correlate with better functional states in patients. Therefore, a reduction of angiogenin levels in plasma and the exosome fraction from plasma may be a marker of disease progression, but these data need to be confirmed in a larger cohort.

Introduction. Over the past several decades, the study of mutations associated with motor neuron disease has led to the development of a number of transgenic animal models of motor neuron disease. One of the causes of the familial form of this disorder is mutations in the gene encoding Cu/Zn superoxide dismutase 1. The B6SJL-Tg (SOD1*G93A) mouse strain expresses a mutant form of human superoxide dismutase 1. Aim of study. To assess motor functions, dynamics of survival, and morphological changes in the spinal cord of transgenic B6SJL-Tg (SOD1*G93A) mice. Material and methods. In total, 31 animals have been studied. Starting from the age of 22 weeks, once every two weeks, the “open field” and “beam walking” motor tests were performed. The morphological changes in the spinal cord were evaluated at intermediate (26–35 weeks) and late stages (40–45 weeks). Neuronal proteins NeuN and PGP9.5, gliofibrillar protein, cyclonucleotide phosphatase (a marker of oligodendroglia) and a marker protein of microglia IBA1 were detected by immunohistochemistry; antibodies MTC02 to the outer membrane protein were used to detect mitochondria. Results. Motor problems appeared at the age of 24–26 weeks and steadily progressed; one could see consistent paresis of the hindlimbs, then the forelimbs, which was accompanied by general hypotrophy of the animals. There was a greater variability in the timing of symptom onset and life expectancy in males compared to females. The neurodegenerative process with damage to motor neurons was accompanied by the activation of micro- and astroglia. A sharp decrease in immunoreactivity to the mitochondrial marker MTC02 was found. Conclusion. The obtained results demonstrate new details of the development of a complex of motor and pathomorphological changes characteristic of motor neuron disease in B6SJL-Tg (SOD1*G93A) mice. Clarification of the fine dynamics of the neurodegenerative process in these animals is of great importance for monitoring the course of the disease during preclinical trials of new drugs and methods of gene therapy.

In recent years, increasing attention has been paid to the study of the communication between cells in the nervous system with extracellular vesicles, including exosomes, under physiological and pathological conditions. Exosomes are small extracellular vesicles ranging in size from 50 to 200 nm, which are secreted by most cell types and provide communication between cells by transporting proteins, lipids, and RNA to target cells. In addition, they perform antigen-presenting and signaling functions and can act as anti-inflammatory or pro-inflammatory agents. Data has been accumulated on the role of exosomes in the development of the pathological process in nervous system diseases, primarily brain tumors and neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is a progressive fatal disease in which the selective death of motor neurons occurs. ALS inevitably leads to disruption of the functioning of muscles that perform vital functions and death of the patient in several years. The mechanisms that underlie the death of motor neurons and the spread of the pathological process are not clear. It is impossible to predict the rate of disease progression and the probable life expectancy of the patient. The most important mechanisms of AS development include the accumulation of aggregates of pathological proteins in neuronal bodies and impaired RNA metabolism. The possibility of transfer of pathological proteins and other molecules associated with the development of ALS through exosomes has been proven. This review provides an overview of studies on exosomes in different CNS diseases. The mechanisms of progression and spreading of the neurodegenerative process in ALS are discussed, focusing on the roles that exosomes and potential biomarkers of the disease in the exosomal fraction play.

Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401–4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric mean titer 20. Antigen-specific response in peripheral blood mononuclear cells was also detected in 100 % of participants, as well as in CD4+ and CD8+ T cells in 82.8 % and 58.6 % of participants vaccinated at full dose, respectively. The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials. Indeed, the strong immune response to the vaccine may elicit long-term protection. This trial was registered with grls.rosminzdrav.ru (No. 495*), and with zakupki.gov.ru (No. 0373100043215000055).