A Y374X TDP43 truncation leads to an altered fibroblast metabolic profile in amyotrophic lateral sclerosis driven by pyruvate and TCA cycle intermediate alterations

Microarray and metabolomic analysis has been applied to the study of ALS in order to investigate how a Y374X TDP43 truncation mutation leads to an altered metabolic profile in fibroblasts driven by pyruvate and TCA cycle intermediate alterations The aim of the present study is to combine transcriptomics, metabolic flux analysis and protein expression analysis in fibroblasts in order to investigate how the Y34X truncation mutation in the TDP43 gene causes metabolic dysfunction Fibroblasts from three truncation mutation patients, three sporadic ALS cases and three neurologically normal controls were used for transcriptomic analysis