Репозиторий Университета

© 2018 Dynasty Publishing House. All rights reserved. The article presents a clinical case of a patient with genetically confirmed Alagille syndrome (ALGS) with marked delay of physical development that did not correspond to the severity of liver damage. Alagille syndrome (ALGS) is a rare hereditary disease with underlying hypoplasia of the intrahepatic bile ducts manifested by cholestasis syndrome in the first weeks of life. Developmental delay is characteristic for cholestatic diseases of the liver, including ALGS, which is conditioned by impaired absorption of fats and fat-soluble vitamins in the intestines. But growth delay and underweight in this syndrome often do not correlate with the severity of cholestatis syndrome, and causes of their development remain unstudied. Cholestatis syndrome was moderate, and clinical signs of liver cirrhosis were absent. Intense skin itching, greatly disturbing not only the baby's wake period but also sleep, along with marked height and weight deficit were indications for liver transplantation at the age of 4 years, after which a fast normalisation of the parameters of physical development was noted. This clinical case study permits to hypothesize that developmental delay in children with ALGS is conditioned by chronic cholestatic liver damage, irrespective of the severity of its clinical presentation.

© 2018 John Wiley  &  Sons Ltd. While the insulin receptor (IR) was found in the CNS decades ago, the brain was long considered to be an insulin-insensitive organ. This view is currently revisited, given emerging evidence of critical roles of IR-mediated signaling in development, neuroprotection, metabolism, and plasticity in the brain. These diverse cellular and physiological IR activities are distinct from metabolic IR functions in peripheral tissues, thus highlighting region specificity of IR properties. This particularly concerns the fact that two IR isoforms, A and B, are predominantly expressed in either the brain or peripheral tissues, respectively, and neurons express exclusively IR-A. Intriguingly, in comparison with IR-B, IR-A displays high binding affinity and is also activated by low concentrations of insulin-like growth factor-2 (IGF-2), a regulator of neuronal plasticity, whose dysregulation is associated with neuropathologic processes. Deficiencies in IR activation, insulin availability, and downstream IR-related mechanisms may result in aberrant IR-mediated functions and, subsequently, a broad range of brain disorders, including neurodevelopmental syndromes, neoplasms, neurodegenerative conditions, and depression. Here, we discuss findings on the brain-specific features of IR-mediated signaling with focus on mechanisms of primary receptor activation and their roles in the neuropathology. We aimed to uncover the remaining gaps in current knowledge on IR physiology and highlight new therapies targeting IR, such as IR sensitizers.