Subsequent investigation of the TIGAR-upstream regulator p53 and the downstream targets HK-I and HK-II in PD brains suggested a possible mild increase in HK-I.
These results suggested that Glut9 was a functional urate transporter, whose up-regulation by activation of p53 resulted in the increased intracellular urate levels in PD models.
Thus, our study suggests that inhibiting p53 and/or active caspase-3 may be considered as a therapeutic approach to ameliorate PD skeletal muscle abnormalities.
Here, we discuss in detail the various studies demonstrating the importance of the functional interplay between parkin and p53 and its impairment by pathogenic mutations likely contributing to the etiology of PD and gliomas.
Collectively, these observations suggest that the interplay between nucleolar dysfunction and increased oxidative stress, involving p53 and mTOR signaling, may constitute a destructive axis in experimental and sporadic PD.
This review will focus on the clues linking p53 to the etiology of PD and the evidences that this protein may be at the center of multiple signaling cascades not only altered by mutations of various proteins responsible for familial cases of PD but also on more general sporadic cases of this devastating disease.