Regulatory function of praja ring finger ubiquitin ligase 2 mediated by the axis in mouse hippocampal neuronal cells.

Praja2 (), a member of the growing family of mammalian RING E3 ubiquitin ligases, is reportedly involved in not only several types of cancer but also neurological diseases and disorders, but the genetic mechanism underlying the regulation of in the nervous system remains unclear. To study the cellular and molecular functions of in mouse hippocampal neuronal cells (MHNCs), we used gain- and loss-of-function manipulations of in HT-22 cells and tested their regulatory effects on three Alzheimer's disease (AD) genes and cell proliferation. The results revealed that the expression of AD markers, including amyloid beta precursor protein (), microtubule-associated protein tau (), and gamma-secretase activating protein (), could be inhibited by overexpression and activated by knockdown. In addition, HT-22 cell proliferation was enhanced by upregulation and suppressed by its downregulation. We also evaluated and quantified the targets that responded to the enforced expression of by RNA-Seq, and the results showed that purinergic receptor P2X, ligand-gated ion channel 3 and 7 ( and ), which show different expression patterns in the critical calcium signaling pathway, mediated the regulatory effect of in HT-22 cells. Functional studies indicated that regulated HT-22 cells development and AD marker genes by inhibiting but promoting , a gene downstream of . In conclusion, our results provide new insights into the regulatory function of the gene in MHNCs and thus underscore the potential relevance of this molecule to the pathophysiology of AD.