Disaccharide trehalose in experimental therapies for neurodegenerative disorders: Molecular targets and translational potential.

Induction of autophagy is a prospective approach to the treatment of neurodegeneration. In the recent decade, trehalose attracted special attention. It is an autophagy inducer with negligible adverse effects and is approved for use in humans according to FDA requirements. Trehalose has a therapeutic effect in various experimental models of diseases. This glucose disaccharide with a flexible α-1-1'-glycosidic bond has unique properties: induction of mTOR-independent autophagy (with kinase AMPK as the main target) and a chaperone-like effect on proteins imparting them natural spatial structure. Thus, it can reduce the accumulation of neurotoxic aberrant/misfolded proteins. Trehalose has an anti-inflammatory effect and inhibits detrimental oxidative stress partially owing to the enhancement of endogenous antioxidant defense represented by the Nrf2 protein. The disaccharide activates lysosome and autophagosome biogenesis pathways through the protein factors TFEB and FOXO1. Here we review various mechanisms of the neuroprotective action of trehalose and touch on the possibility of pleiotropic effects. Current knowledge about specific features of trehalose pharmacodynamics is discussed. The neuroprotective effects of trehalose in animal models of major neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases are examined too. Attention is given to translational transition to clinical trials of this drug, especially oral and parenteral routes of administration. Besides, the possibility of enhancing the therapeutic benefit via a combination of mTOR-dependent and mTOR-independent autophagy inducers is analyzed. In general, trehalose appears to be a promising multitarget tool for the inhibition of experimental neurodegeneration and requires thorough investigation of its clinical capabilities.

Opening up new horizons for psychiatric genetics in the Russian Federation: moving toward a national consortium.

We provide an overview of the recent achievements in psychiatric genetics research in the Russian Federation and present genotype-phenotype, population, epigenetic, cytogenetic, functional, ENIGMA, and pharmacogenetic studies, with an emphasis on genome-wide association studies. The genetic backgrounds of mental illnesses in the polyethnic and multicultural population of the Russian Federation are still understudied. Furthermore, genetic, genomic, and pharmacogenetic data from the Russian Federation are not adequately represented in the international scientific literature, are currently not available for meta-analyses and have never been compared with data from other populations. Most of these problems cannot be solved by individual centers working in isolation but warrant a truly collaborative effort that brings together all the major psychiatric genetic research centers in the Russian Federation in a national consortium. For this reason, we have established the Russian National Consortium for Psychiatric Genetics (RNCPG) with the aim to strengthen the power and rigor of psychiatric genetics research in the Russian Federation and enhance the international compatibility of this research.The consortium is set up as an open organization that will facilitate collaborations on complex biomedical research projects in human mental health in the Russian Federation and abroad. These projects will include genotyping, sequencing, transcriptome and epigenome analysis, metabolomics, and a wide array of other state-of-the-art analyses. Here, we discuss the challenges we face and the approaches we will take to unlock the huge potential that the Russian Federation holds for the worldwide psychiatric genetics community.

Diagnosis and Management of Autism Spectrum Disorders in Russia: Clinical-Biological Approaches.

The study describes the latest recommended and adopted clinical and management practice for children and adults with autistic spectrum disorder (ASD) in Russia and discusses the most recent research work by Russian clinicians and neuroscientists in the field. The study also presents data from the first epidemiological studies on ASD prevalence and explores the latest recommendations for clinical-biological assessments for ASD diagnosis and management in Russia. The authors call for collaboration of experts in ASD field to exchange clinical and research ideas between professionals from Russia and Western European countries and expand our mutual knowledge about ASD. This should include clinical and neurobiological studies aiming to develop differential rational approaches for ASD individual management throughout lifespan of these affected individuals.

Leukocyte elastase and autoantibodies to nerve growth factor in the acute phase of schizophrenia and their relationship to symptomatology.

Many investigations suggest that abnormalities of the immune system are involved in the pathophysiology of schizophrenia. We recently found increased activity of leukocyte elastase (LE) and elevated levels of autoantibodies to neurospecific protein - nerve growth factor (Aab to NGF) - products of the innate and adaptive arms of the immune system in the serum of patients with acute stage schizophrenia. The aim of this study is to elucidate whether or not the changes of LE activity and Aab to NGF level are related to prominent features of schizophrenia. Patients (n=71) corresponding to ICD-10 criteria for relapse-remitting schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS). Patients with predominantly positive symptoms showed significantly elevated serum levels of Aab to NGF compared to patients with predominantly negative symptoms, who were more likely to exhibit the high LE activity. Moreover, progression of positive symptoms was coupled with gradual increase of Aab to NGF level and reduction of LE activity. Based on these findings we conclude that the high levels of Aab to NGF relate to a clinical picture characterised mainly by positive symptoms of schizophrenia, whereas high LE-activities relate to a clinical picture with mainly negative symptoms of schizophrenia.