Abstract
Degeneration of dopaminergic (DA) neurons in the brain is the major cause for Parkinson’s disease (PD). While genetic loci and cellular pathways involved in DA neuron proliferation have been well documented, the genetic and molecular and cellular basis of DA cell survival remains to be elucidated. Recently, studies aimed to uncover the mechanisms of DA neural protection and regeneration have been reported. One of the most recent discoveries, i.e., multi-function of human oncogene SCL/TAL interrupting locus (Stil) in DA cell proliferation, neural protection, and regeneration, created a new field for studying DA cells and possible treatment of PD. In DA neurons, Stil functions through the Sonic hedgehog (Shh) pathway by releasing the inhibition of SUFU to GLI1, and thereby enhances Shh-target gene transcription required for neural proliferation, protection, and regeneration. In this review article, we will highlight some of the new findings from researches relate to Stil in DA cells using zebrafish models and cultured mammalian PC12 cells. The findings may provide the proof-of-concept for the development of Stil as a tool for diagnosis and/or treatment of human diseases, particularly those caused by DA neural degeneration.
Highlights
The SCL/TAL interrupting locus (Stil) is a human oncogene that was originally identified from human T-cell lymphoblastic leukemia, where it functions as a hematopoietic transcription factor[1]
In summary, this paper provides evidence that through the Sonic hedgehog (Shh) signaling transduction pathway the human oncogene Stil plays novel roles in DA cells
Considering the conserved roles of Stil in cell proliferation, the involvement of Stil in the Shh pathway, and the effect of Shh signaling in drug resistance, it is conceivable that Stil may function as an ON-OFF switch that controls the outcome of Shh signaling transduction, which in turns, regulates the fate of individual cell groups, for example, to be developed or undergo apoptosis
Summary
The SCL/TAL interrupting locus (Stil) is a human oncogene that was originally identified from human T-cell lymphoblastic leukemia, where it functions as a hematopoietic transcription factor[1]. To investigate if the expression of Stil is required for maintaining the DA cells (e.g., whether or not the decrease of DA cells in nbb mutants is due to age-related neural degeneration), Li et al.[17] examined the survival of DA neurons in zebrafish retinas in response to treatment with DA-specific neurotoxins, such as 6hydroxydopamine (6-OHDA)[33,34].
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