Role of the von Hippel-Lindau Tumor Suppressor Protein in Neuronal Differentiation of Somatic Stem Cells and its Application to Neuronal Regeneration: A Review - Abstract
von Hippel-Lindau tumor suppressor (VHL) protein functions to cause somatic stem cells to differentiate into neurons. Not only VHL protein but also a peptide derived from it shows this capability of eliciting neuronal differentiation by somatic stem cells. Up to now, rodent neural stem cells (NSCs) and human hair follicle stem cells, both of which are derived from ectoderm, have been shown to undergo neuronal differentiation triggered by VHL protein or a peptide derived from it. In addition, rodent skin-derived precursors and rodent bone marrow mesenchymal stem cells, both of which are derived from mesenchyme, also can differentiate into neurons by the same method. A 15-amino-acid peptide derived from VHL protein corresponds to the part of the sequence of VHL that binds to elongin C, which sequence is considered to be a domain for neuronal differentiation. The mechanism of neuronal differentiation of somatic stem cells by VHL is suggested to be inhibition of Stat 3. When VHL protein or oligopeptide derived from it was transferred into somatic stem cells and these cells were transplanted into the central nervous system of animals modeling a neuronal disease, the implanted cells differentiated into neuronal cells, resulting in recovery of neuronal functions. These facts suggest that somatic stem cells with transferred VHL protein or oligopeptide derived from it are candidates of donor cells for regeneration therapy of intractable neuronal diseases.