We have asked whether p75(NTR) may play a role in neuronal apoptosis by producing transgenic mice that express the p75(NTR) intracellular domain within peripheral and central neurons. These animals showed profound reductions in numbers of sympathetic and peripheral sensory neurons as well as cell loss in the neocortex, where there is normally little or no p75(NTR) expression. Developmental loss...

Alzheimer’s disease is a neurodegenerative disorder characterized by the extracellular deposition in the brain of aggregated b -amyloid peptide, presumed to play a pathogenic role, and by preferential loss of neurons that express the 75-kD neurotrophin receptor (p75 NTR ). Using rat cortical neurons and NIH-3T3 cell line engineered to stably express p75 NTR , we find that the b -amyloid peptide...

Neurotrophin receptor p75 (p75) knockout mice (p75 (−/−) mice) provide a good animal model of progressive-onset hearing loss. Cell loss of the spiral ganglion neurons (SGNs) and hair cell degeneration at the basal turn of the cochlea are seen in p75(−/−) mice from 3 months of age. Furthermore, from 3 to 6 months of age, the hearing thresholds of p75(−/−) mice are gradually raised; and after 6 m...

Nerve growth factor binds to the TrkA and p75(NTR) (p75) and generates signals leading to neuronal cell survival, differentiation, and programmed cell death. Here we describe a series of experiments involving selective activation of either TrkA or p75 in which distinct cell-signaling intermediates promote different cellular consequences. We analyzed pheochromocytoma 12 (PC12) cells stably expre...

BACKGROUND As Lens epithelium-derived growth factor (LEDGF/p75) is an important co-factor involved in HIV-1 integration, the LEDGF/p75-IN interaction is a promising target for the new class of allosteric HIV integrase inhibitors (LEDGINs). Few data are available on the genetic variability of LEDGF/p75 and the influence on HIV disease in vivo. This study evaluated the relation between LEDGF/p75 ...

Activation of the neurotrophin receptor p75 has been shown to elicit opposing cellular signals. Depending on the context of the cell, p75 will either promote survival or induce apoptosis after neurotrophin stimulation. p75-induced apoptosis occurs through activation of c-Jun N-terminal kinase (JNK), whereas the survival signal is mediated by nuclear factor kappaB (NFkappaB). The receptor proxim...

Lorentz CU, Alston EN, Belcik T, Lindner JR, Giraud GD, Habecker BA. Heterogeneous ventricular sympathetic innervation, altered -adrenergic receptor expression, and rhythm instability in mice lacking the p75 neurotrophin receptor. Am J Physiol Heart Circ Physiol 298: H1652–H1660, 2010. First published February 26, 2010; doi:10.1152/ajpheart.01128.2009.—Sympathetic nerves stimulate cardiac funct...

Ligand-mediated dimerization has emerged as a universal mechanism of growth factor receptor activation. Neurotrophins interact with dimers of the p75 neurotrophin receptor (p75(NTR)), but the mechanism of receptor activation has remained elusive. Here, we show that p75(NTR) forms disulphide-linked dimers independently of neurotrophin binding through the highly conserved Cys(257) in its transmem...

Basal forebrain GABAergic and cholinergic circuits regulate the activity of cholinergic projections to the cortex and hippocampus. Because these projections influence cortical development and function, the development of basal forebrain excitatory and inhibitory neurons is critical for overall brain development. We show that the neurotransmitter phenotype of these neurons is developmentally reg...

The neurotrophin plays an important role in the development, differentiation and survival of the nervous system in vertebrates. It exerts its cellular effects through two different receptors, the Trk receptor tyrosine kinase neurotrophin receptor and the p75 neurotrophin receptor, a member of the tumor necrosis factor receptor superfamily. Trk and p75 neurotrophin receptors utilize specific tar...