Insights into the molecular mechanisms of methylmalonic acidemia using microarray technology.

Methylmalonic acidemia (MMA) is widely considered as an autosomal recessive metabolic disorder that results in accumulation of high levels of methylmalonic acid and eventually brain damage. This study aims to investigate the effects of methylmalonic acid on neurons and analyze various gene expression profiles in rat cortical neurons treated with methylmalonic acid in order to understand the effects of MMA. High concentrations of methylmalonic acid could significantly alter the morphology of rat cortical neurons, attenuate cell viability and aggravate cell apoptosis. Moreover, 564 differentially expressed genes were identified by microarray analysis. A considerable number of these genes were apoptosis-related genes. Enrichment analysis of the apoptosis-related genes revealed that the MAPK and p53 signaling pathways may be involved in the pathogenesis of MMA. Our results together reveal that methylmalonic acid plays a critical role in neuron damage and that the MAPK and p53 signaling pathways may be involved in the mechanism of MMA.