Редактирование: SV2B (раздел)

==Publications==

{{medline-entry
|title=Mutant Huntingtin Causes a Selective Decrease in the Expression of Synaptic Vesicle Protein 2C.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29713895
|abstract=Huntington's disease (HD) is a neurodegenerative disease caused by a polyglutamine expansion in the huntingtin (Htt) protein. Mutant Htt causes synaptic transmission dysfunctions by interfering in the expression of synaptic proteins, leading to early HD symptoms. Synaptic vesicle proteins 2 (SV2s), a family of synaptic vesicle proteins including 3 members, [[SV2A]], [[SV2B]], and [[SV2C]], plays important roles in synaptic physiology. Here, we investigated whether the expression of SV2s is affected by mutant Htt in the brains of HD transgenic ([[TG]]) mice and Neuro2a mouse neuroblastoma cells (N2a cells) expressing mutant Htt. Western blot analysis showed that the protein levels of [[SV2A]] and [[SV2B]] were not significantly changed in the brains of HD [[TG]] mice expressing mutant Htt with 82 glutamine repeats. However, in the [[TG]] mouse brain there was a dramatic decrease in the protein level of [[SV2C]], which has a restricted distribution pattern in regions particularly vulnerable in HD. Immunostaining revealed that the immunoreactivity of [[SV2C]] was progressively weakened in the basal ganglia and hippocampus of [[TG]] mice. RT-PCR demonstrated that the mRNA level of [[SV2C]] progressively declined in the [[TG]] mouse brain without detectable changes in the mRNA levels of [[SV2A]] and [[SV2B]], indicating that mutant Htt selectively inhibits the transcriptional expression of [[SV2C]]. Furthermore, we found that only [[SV2C]] expression was progressively inhibited in N2a cells expressing a mutant Htt containing 120 glutamine repeats. These findings suggest that the synaptic dysfunction in HD results from the mutant Htt-mediated inhibition of [[SV2C]] transcriptional expression. These data also imply that the restricted distribution and decreased expression of [[SV2C]] contribute to the brain region-selective pathology of HD.
|mesh-terms=* Aging
* Animals
* Brain
* Cell Line, Tumor
* Gene Expression
* Huntingtin Protein
* Membrane Glycoproteins
* Mice
* Mice, Transgenic
* Mutation
* Nerve Tissue Proteins
* RNA, Messenger
* Transcription, Genetic
|keywords=* Basal ganglia
* Hippocampus
* Huntington’s disease
* Synaptic vesicle protein 2C
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129247
}}