Regulation of global gene expression in brain by TMP21

TMP21, a type I transmembrane protein of thep24 protein family, mediates protein trafficking and maturation. Dysregulation of TMP21 is implicated in the pathogenesis of Alzheimer’s disease (AD). However, underlying mechanisms remain elusive. To reveal the function of TMP21 in the brain and the pathogenic role of TMP21 in the brain of AD, the global gene expression was profiled in the brain of TMP21 knockdown mice. We found that 8196 and 8195 genes are significantly altered in the hippocampus and cortex, respectively. The genes are involved in a number of brain function-related pathways, including glutamatergic synapse pathway, serotonergic synapse pathway, synaptic vesicle pathway, and long-term depression pathway. Moreover, the network analysis suggests that the TMP21 may contribute to the pathogenesis of AD by regulatingPI3K/Akt/GSK3β signalling pathway. Our study provides an insight into the physiological function of TMP21 in the brain and pathological role of TMP21 in AD.