ABSTRACT
Huntington's disease is a hereditary neurodegenerative disease that primarily affects striatal neurons. Recent studies demonstrated abnormalities in calcium regulation in striatal neurons in Huntington's disease, which leads to elimination of synaptic connections between cortical and striatal neurons. In the present study, we focused on the neuroprotective properties of σ1-receptor, because one of its main functions is associated with modulation of calcium homeostasis in cells. The application of selective σ1-receptor agonists to the corticostriatal cell culture restores synaptic connections between the cortical and striatal neurons. Based on the obtained data, we assume that σ1-receptor is a promising target for the development of drugs for the therapy of Huntington's disease.
Subject(s)
Calcium/metabolism , Huntington Disease/genetics , Neurons/metabolism , Receptors, sigma/genetics , Synaptic Transmission/genetics , Animals , Anisoles/pharmacology , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Corpus Striatum/metabolism , Dendritic Spines/metabolism , Dendritic Spines/pathology , Gene Expression , Homeostasis , Huntington Disease/metabolism , Huntington Disease/pathology , Male , Mice , Models, Biological , Morpholines/pharmacology , Neurons/pathology , Piperidines/pharmacology , Primary Cell Culture , Propylamines/pharmacology , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Receptors, sigma/agonists , Receptors, sigma/antagonists & inhibitors , Receptors, sigma/metabolism , Synapses/metabolism , Synapses/pathology , Transduction, Genetic , Sigma-1 ReceptorABSTRACT
Alpha-actinin 1 and alpha-actinin 4 belong to a family of actin-binding proteins with shared structural function and regulation of several processes in a cell. Based on previous data on different distribution of these proteins in the nucleus and cytoplasm, we have explored in detail the distribution of alpha-actinin 1 and alpha-actinin 4 in subcellular fractions in A431 cells spread on fibronectin. Several methods of subcellular fractionation were used. Complex approach allowed resuming that revealing of alpha-actinin isoforms in fractions depended on the composition of lysis buffer and preliminary low-temperature freezing of the cells. We have drawn a conclusion that alpha-actinin 4 can be found in all cytoplasmic and nuclear subfractions, while alpha-actinin 1 is characterized by cytoplasmic and membrane localization with specificity of its distribution tightly to the nuclear membrane.
