Новые подходы в исследовании молекулярного патогенеза спиноцеребеллярной атаксии 2-го типа

Abstract

Spinocerebellar ataxia type 2 (SCA2) represents a progressive hereditary disease, genetically caused by a polyglutamine expansion in the ataxin-2 protein. The effective ways of the therapeutic treatment as well as the disease-modifiyng therapy are not available yet for SCA2 patients. At present, patients can get only the symptomatic treatment or palliative care. Many research groups study the physiological, molecular, and biochemical changes in the cerebellar neurons from SCA2 patients and different model systems to find new therapeutic targets for SCA2 treatment. Comprehensive approaches in the research of SCA2 pathogenesis allowed to get the new data about the molecular mechanism of the disease and to suggest the possible strategies for the potential therapy of the disease. In this article the relevant data about the genetic basis of SCA2 are summarized, the known to date properties and functions of ataxin-2 protein are described, the mechanisms of the cerebellar cells degeneration are discussed together with the dicturbances of the cellular physilological functions and the related impairments of the cerebellar curcuits, the information about the modern model systems that allow to study the SCA2 bases is presented, and also the data about new approaches in molecular mechanism research are presented, describing the SCA2 pathology bases such as aggregation, oxidative stress, the dysfunction of the cell and calcium signaling. The role of the autophagy and microglia in the molecular pathogenesis of SCA2 is also discussed.