Diverse functions of the p75 neurotrophin receptor

Abstract

The pan-neurotrophin receptor p75NTR belongs to a large family of receptors, which includes tumor necrosis factor receptors, Fas and approximately 25 other members. The p75NTR is the first receptor to be cloned molecularly. Recent years have seen the emergence of a consensus regarding the signaling pathways activated by p75NTR and its potential biological function, although receptor characterization had not been targeted for some years. We now know that p75NTR has surprisingly diverse effects, ranging from cell death to regulation of axon elongation. This diversity can be explained by the complex formation of p75NTR with other receptors and multiple signaling molecules that interact with the intracellular domain of p75NTR.

Caffeic acid phenethyl ester (CAPE) protects PC12 cells from MPP+ toxicity by inducing the expression of neuron-typical proteins

“…Therefore, our study is in line with previous studies which demonstrated (i) that CAPE protects nigral dopaminergic neurons via induction of brain-derived neurotrophic factor (BDNF) (Kurauchi et al, 2012) and (ii) induces the expression of NGF and p75 neurotrophin receptor (p75 NTR ) in C6 glioma cells (Lin et al, 2010b). NGF binding to p75 NTR has been associated with both neuronal survival and death, and the balance of these opposing effects is important in the development, maintenance and regeneration of the nervous system (Yamashita et al, 2005). Analytical and experimental conditions were described in Section 2.…”

Mice lacking the p75 receptor fail to acquire a normal complement of taste buds and geniculate ganglion neurons by adulthood

“…The role of p75 is enigmatic primarily because this receptor interacts with such a diverse group of molecules, resulting in a large array of downstream events (for review, see Huang and Reichardt, 2001;Bronfman and Fainzilber, 2004;Yamashita et al, 2005a). For example, the p75 receptor has been shown to enhance neuron survival in some instances (Stucky and Koltzenburg, 1997;DeFreitas et al, 2001;Song and Posse de Chaves, 2003) and to mediate cell death in others (Agerman et al, 2000;Botchkarev et al, 2000;Lee et al, 2001;Troy et al, 2002).…”

The simple truth is seldom true and never simple

“…10 The intracellular signaling pathways activated by p75 NTR can be subdivided into 3 broad categories: (1) pathways that lead to apoptosis, which include the NRIF/ TNF receptor-associated factor/Rac/c-Jun N-terminal kinase pathway; (2) pathways that promote cell survival, which include nuclear factor-B, phosphoinositide 3-kinase/Akt, and Ras/mitogen-activated protein kinase; and (3) pathways that modulate the cytoskeleton and lead to cellular regeneration, such as the RhoA/Rho kinase pathway. 7,10 Which are the target cells for NTs in the liver? Part of the truth was unveiled by Trim et al who reported that activated hepatic stellate cells carry p75 NTR and undergo apoptosis in response to NGF secreted by neighboring regenerating hepatocytes.…”

“…10 Finally, p75 NTR can also signal in the absence of ligands, presumably when the receptor oligomerizes, or when it forms other complexes. 10 The intracellular signaling pathways activated by p75 NTR can be subdivided into 3 broad categories: (1) pathways that lead to apoptosis, which include the NRIF/ TNF receptor-associated factor/Rac/c-Jun N-terminal kinase pathway; (2) pathways that promote cell survival, which include nuclear factor-B, phosphoinositide 3-kinase/Akt, and Ras/mitogen-activated protein kinase; and (3) pathways that modulate the cytoskeleton and lead to cellular regeneration, such as the RhoA/Rho kinase pathway. 7,10 Which are the target cells for NTs in the liver?…”