Ruolo della proteina CSB nei meccanismi di neurogenesi adulta e neuroprotezione
Author(s)
Ciaffardini, Flavia
Date Issued
May 31, 2013
Type
Doctoral Thesis
Abstract
Cockayne syndrome (CS) is a progressive developmental and neurodegenerative disorder that results in premature death during childhood. Most of the patients are mutated in the CSB gene. Although the genetic basis has been established for this disease, the precise molecular cause for neurodegeneration is not entirely clear. The present study was designed to verify whether or not CSB plays a critical role in survival, self-renewal and differentiation capabilities of neural stem/progenitor cells under normal and hypoxic conditions. Our innovative approach makes use of human neural progenitor cell system that is endowed with efficient self-renewal and multi-lineage differentiation capabilities. First we demonstrated that CSB knockdown in neural stem cell showed a dramatic reduction in survival and self-renewal capabilities, a feature which appears to be particularly enhanced under hypoxic condition. Further, CSB knockdown also dramatically reduced the differentiation potential of neural stem/progenitor cells. Along this line, neurite outgrowth, which is a characteristic feature of differentiating neurons, was dramatically affected in CSB silenced cells. Interestingly, CSB protein which is induced during neural differentiation, appear to play a double role during neuronal differentiation: in the nucleus it modulates the transcriptional programs that govern survival and differentiation of neural stem cells, second, in the cytoplasm it participates in the mechanism that orchestrate neurite outgrowth and retrograde axonal transport. Collectively, though currently in progress, this study suggests that CSB is a critical factor for protecting the functional integrity of neural stem/progenitor cells in self-renewal and differentiation processes.
Additional information
Dottorato di ricerca in Genetica e biologia cellulare
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