Huwe1: A possible role in PD

Abstract

1 The following work was supported from MERC, Mansoura University, Egypt. Sir, Several strategies have been proposed for treating Parkinson’s disease, including direct cell replacement [1]. Recent studies revealed that the conversion of NSCs to appropriate nigral DA neurons has proven relatively unsatisfactory. The understanding of the molecular circuitry of reprogramming will provide new targets that could improve this field. The HECT domain E3 ubiquitin ligase (Huwe1) seems to play a critical role in promoting neurogenesis [2]. The transcription factor N-Myc maintains the proliferation of precursor cells in the nervous system. Previous studies have revealed that N-Myc undergoes proteasome-dependent degradation. E3 ubiquitin ligase Huwe1 has been demonstrated as a new NMyc-interacting protein [2]. Huwe1 triggered the polyubiquitination and subsequent degradation of N-Myc [3]. To determine the functional consequence of Huwe1-mediated degradation of NMyc in ES cells, wild-type and Huwe1 knockout ES cells were placed in differentiating conditions. While differentiated wild-type ES cells expressed neuronal genes, e.g. neurogenin, Huwe1 knockout ES cells failed to do so [4,5]. Furthermore, knockout of Huwe1 in ES cells led to the accumulation of N-Myc protein. Huwe1 acts in a critical developmental window to target N-Myc for degradation and to induce neurogenesis [6,7]. Based on the previous data, we propose that new techniques – e.g. siRNA – targeting Huwe1 can affect neurogenesis, hence, improving repair of damaged areas in case of PD.