Modulation of the generation of dopaminergic neurons from human neural stem cells by Bcl-X(L): mechanisms of action

Abstract

Understanding the developmental mechanisms governing dopaminergic neuron generation and maintenance is crucial for the development of neuronal replacement therapeutic procedures, like in Parkinson's disease (PD), but also for research aimed at drug screening and pharmacology. In the present chapter, we review the present situation using stem cells of different origins (pluripotent and multipotent) and summarize current manipulations of stem cells for the enhancement of dopaminergic neuron generation, focusing on the actions of Bcl-X(L). Bcl-X(L) not only enhances dopaminergic neuron survival but also augments the expression of key developmental and maintenance genes, and, through the lengthening of the cell cycle early during differentiation, regulates cell fate decisions, producing a net enhancement of neurogenesis. The relevance of these findings is discussed in the context of basic neurogenesis and also for the development of efficient cell therapy in PD.