Aggregation-prone A53T mutant of α-synuclein exaggerates methamphetamine neurotoxicity in SH-SY5Y cells: Protective role of cellular cholesterol.

ABSTRACT: The aim of this study is to examine the effects of wild type as well as a mutant (A53T) form of α-synuclein (α-syn) on neuronal cells exposed to methamphetamine (METH). SH-SY5Y human dopaminergic neuronal cells stably expressing exogenously added wild type (WT) or A53T α-syn were established for this purpose. Among the three types of cells, parental, WT α-syn-overexpressing, and A53T α-syn overexpressing SH-SY5Y cells (hereafter referred to as SH-SY5Y, WT SH-SY5Y, and A53T SH-SY5Y, respectively), only A53T SH-SY5Y cells showed significant loss of cell viability after exposure to 2 mM METH for 24 h. Transcriptome analysis using DNA microarray showed that METH induced genes for cholesterol biosynthesis in all of these three cell lines, suggesting that METH upregulates cellular cholesterol bi

SUBMITTER: Aoki S 

PROVIDER: S-EPMC9742969 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature