The effect of neuronal insult on neurotrophin receptor expression and signalling

Abstract

The neurotrophins were initially identified as a group of target-derived neuronal factors but have since been shown to mediate a wide range of biological functions including cell survival, maintenance, differentiation and apoptosis. These diverse functions are mediated via two types of receptor: the tropomyosin-related kinase (Trk) receptor tyrosine kinases which are traditionally known as the high- affinity neurotrophin receptors, and the low-affinity p75 neurotrophin receptor (p75NTR). The Trk receptors transmit positive signals such as enhanced growth and survival, while the p75NTR is somewhat of a biological paradox in that it has been shown to transmit both positive and negative signals. Increased expression of the p75NTR has been observed post injury and in neurodegenerative conditions and its expression has been associated with increased cell death. The aim of this study is primarily to assess the role of the p75NTR following neuronal insult in vivo and to establish reliable models by which expression of the p75NTR can be successfully upregulated.