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The development of specific connections between neurons and their targets is determined in part by selective pathway choices made by growing axons, which are directed by guidance factors present in […]

Nerve growth factor (NGF) is a neurotrophic factor secreted by cells that are the targets of innervation of sympathetic and some sensory neurons. However, the mechanism by which the NGF signal is propagated from the axon terminal to the cell body, which can be more than 1 meter away, to influence biochemical events critical for growth and survival of neurons has remained unclear. An NGF-mediated signal transmitted from the terminals and distal axons of cultured rat sympathetic neurons to their nuclei regulated phosphorylation of the transcription factor CREB (cyclic adenosine monophosphate response element-binding protein). Internalization of NGF and its receptor tyrosine kinase TrkA, and their transport to the cell body, were required for transmission of this signal. The tyrosine kinase activity of TrkA was required to maintain it in an autophosphorylated state upon its arrival in the cell body and for propagation of the signal to CREB within neuronal nuclei. Thus, an NGF-TrkA complex is a messenger that delivers the NGF signal from axon terminals to cell bodies of sympathetic neurons., The growth and survival of many populations of neurons depends on trophic support provided by their target tissue[1]. NGF is secreted by targets of sympathetic and some sensory neurons, and [...]

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) selectively bind to distinct members of the Trk family of tyrosine kinase receptors, but all three bind with similar affinities to the neurotrophin receptor p75 ([p75.sup.NTR]). The biological significance of neurotrophin binding to [p75.sup.NTR] in cells that also express Trk receptors has been difficult to ascertain. In the absence of TrkA, NGF binding to [p75.sup.NTR] activated the transcription factor nuclear factor kappa B (NF-kB) in rat Schwann cells. This activation was not observed in Schwann cells isolated from mice that lacked [p75.sup.NTR]. The effect was selective for NGF; NF-kB was not activated by BDNF or NT-3., The best established role for neurotrophins, which include NGF, BDNF, NT-3, NT-4/5, and NT-6, is their ability to support the survival and differentiation of neurons. Three tyrosine kinase receptors, referred [...]

Nerve growth factor (NGF) induces both differentiation and survival of neurons by binding to the Trk receptor protein tyrosine kinase. Although Ras is required for differentiation, it was not required for NGF-mediated survival of rat pheochromocytoma PC-12 cells in serum-free medium. However, the ability of NGF to prevent apoptosis (programmed cell death) was inhibited by wortmannin or LY294002, two specific inhibitors of phosphatidylinositol (Pl)-3 kinase. Moreover, platelet-derived growth factor (PDGF) prevented apoptosis of PC-12 cells expressing the wild-type PDGF receptor, but not of cells expressing a mutant receptor that failed to activate PI-3 kinase. Cell survival thus appears to be mediated by a PI-3 kinase signaling pathway distinct from the pathway that mediates differentiation., Apoptosis plays a key role in the normal development of the nervous system. Up to 50% of many types of developing neurons are eliminated by apoptosis (1). The survival of [...]

Ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) each promote the survival and differentiation of developing motor neurons, but do so through distinct cellular signaling pathways. Administration of either factor alone has been shown to slow, but not to arrest, progression of motor neuron dysfunction in wobbler mice, an animal model of motor neuron disease. Because CNTF and BDNF are known to synergize in vitro and in ovo, the efficacy of CNTF and BDNF cotreatment was tested in the same animal model. Subcutaneous injection of the two factors on alternate days was found to arrest disease progression in wobbler mice for 1 month, as measured by several behavioral, physiological, and histological criteria., The cytokine CNTF promotes the survival and differentiation of developing motor neurons in culture (1), rescues developing chicken motor neurons from death in ovo, and retards axotomy-induced death of facial [...]

Nerve growth factor (NGF) binding to cellular receptors is required for the survival of some neural cells. In contrast to Trk A, the high-affinity NGF receptor that transduces NGF signals for survival and differentiation, the function of the low-affinity NGF receptor, [p75.sup.NGFR], remains uncertain. Expression of [p75.sup.NGFR] induced neural cell death constitutively when [p75.sup.NGFR] was unbound; binding by NGF or monoclonal antibody, however, inhibited cell death induced by [p75.sup.NGFR]. Thus, expression of [p75.sup.NGFR] may explain the dependence of some neural cells on NGF for survival. These findings also suggest that [p75.sup.NGFR] has some functional similarities to other members of a superfamily of receptors that include tumor necrosis factor receptors, Fas (Apo-1), and CD40., Growth factors such as NGF enhance the survival of cells displaying the appropriate receptors. The effects of NGF are mediated at least in part by Trk A, the high-affinity NGF [...]

THE DEVELOPMENT OF THE VERTEBRATE nervous system is characterized by a series of complex events that cause the apparently homogenous neuroepithelium of the early embryo to form the diverse, highly [...]

THE MEMBERS OF THE TRK GENE family [1] code for receptor-like, tyrosine kinase molecules that are transcribed in a pattern that suggests that they have a specialized role in neural [...]

Neurotrophin-3: A Neurotrophic Factor Related to NGF and BDNF WIDESPREAD NEURONAL CELL DEATH ACCOMPANIES normal development of the central and peripheral nervous systems, and apparently plays a crucial role in [...]

Nerve growth factor (NGF) is required for the maturation and survival of sympathetic neurons, but the mechanisms controlling expression of the NGF receptor in developing neuroblasts have not been defined. [...]

NGF and Alzheimer's: Hopes and Fears RESEARCHERS MAY BE ON THE VERGE of beginning a new era in the treatment of degenerative brain diseases such as Alzheimer's. They are moving, [...]

Neurotrophins such as brain-derived neurotrophic factor (BDNF) are thought to be transferred from post- to presynaptic neurons and to be involved in the formation and plasticity of neural circuits. However, direct evidence for a transneuronal transfer of BDNF and its relation to neuronal activity remains elusive. We simultaneously injected complementary DNAs of green fluorescent protein (GFP)-tagged BDNF and red fluorescence protein into the nucleus of single neurons and visualized expression, localization, and transport of BDNF in living neurons. Fluorescent puncta representing BDNF moved in axons in the anterograde direction, though some moved retrogradely, and transferred to postsynaptic neurons in an activity-dependent manner., Neuronal activity modifies the formation of neural circuits in developing cerebral cortex (1-3). Neurotrophins such as BDNF are attractive candidates for molecular signals that translate neuronal activity into such structural [...]

TR3, an immediate-early response gene and an orphan member of the steroid-thyroid hormone-retinoid receptor superfamily of transcription factors, regulates apoptosis through an unknown mechanism. In response to apoptotic stimuli, TR3 translocates from the nucleus to mitochondria to induce cytochrome c release and apoptosis. Mitochondrial targeting of TR3, but not its DNA binding and transactivation, is essential for its proapoptotic effect. Our results reveal a mechanism by which a nuclear transcription factor translocates to mitochondria to initiate apoptosis., The orphan receptor TR3 (also known as nur77 or nerve growth factor--induced clone B NGFI-B) (1-3) functions as a nuclear transcription factor in the regulation of target gene expression (4-7). [...]

Nerve growth factor (NGF) and other neurotrophins support survival of neurons through processes that are incompletely understood. The transcription factor CREB is a critical mediator of NGF-dependent gene expression, but whether CREB family transcription factors regulate expression of genes that contribute to NGF-dependent survival of sympathetic neurons is unknown. CREB-mediated gene expression was both necessary for NGF-dependent survival and sufficient on its own to promote survival of sympathetic neurons. Moreover, expression of Bcl-2 was activated by NGF and other neurotrophins by a CREB-dependent transcriptional mechanism. Overexpression of Bcl-2 reduced the death-promoting effects of CREB inhibition. Together, these data support a mode[ in which neurotrophins promote survival of neurons, in part through a mechanism involving CREB family transcription factor-dependent expression of genes encoding prosurvival factors., Nerve growth factor (NGF), a member of the neurotrophin family of growth factors, is a target-derived survival factor for developing sympathetic neurons (1). CREB [cyclic adenosine monophosphate (cAMP) response element [...]

Learning and memory depend on the persistent modification of synapses between brain neurons. New memories are formed in the hippocampus, which is situated beneath the cerebral cortex, and damage to [...]

Grafting Genetically Modified Cells to the Damaged Brain: Restorative Effects of NGF Expression CONSIDERABLE EFFORT IN RECENT years has been applied toward the development of methods for the genetic modification [...]

Functional Interaction and Partial Homology Between Human Immunodeficiency Virus and Neuroleukin DEMENTIA IN PATIENTS WITH THE acquired immune deficiency syndrome (AIDS) is characterized by poor memory, inability to concentrate, apathy, [...]

The Nerve Growth Factor 35 Years Later THIS FEELING OF FRUSTRATION SO INCISIVELY CONVEYED by these considerations by P. Medawar (1), in the passage quoted above, pervaded, in the forties, [...]

Nerve Growth Factor Gene Expression in the Developing Rat Brain THE RELEASE OF DIFFUSIBLE TROPHic factors by nerve cells and their targets has been thought to play a major role [...]

A Protein Induced During Nerve Growth (GAP-43) Is a Major Component of Growth-Cone Membranes GAP-43 IS ONE OF A SMALL GROUP of axonally transported 'growth-associated' proteins whose synthesis is increased [...]

Gene Transfer and Molecular Cloning of the Human NGF Receptor NERVE GROWTH FACTOR (NGF) and its receptor play an essential role in the survival and maintenance of sympathetic and sensory [...]

Neoplastic transformation is a consequence of the subversion of normal growth regulatory mechanisms. Furthermore, several retroviral oncogenes and their cellular progenitors are intimately associated with the normal processes of proliferation [...]

Trophic factors are soluble molecules that influence the survival and differentiation of neurons in developing animals (1, 2). It has been suggested that abnormalities in the synthesis or utilization of [...]

The development and maintenance of function of the nervous system results from the concerted interaction of a great variety of genetic and epigenetic regulatory mechanisms. Transplantation and ablation experiments performed [...]

The nervous system is made of billions of neurons that are interconnected with astonishing precision. How is genetic information decoded to wire this most complex of computing machines? By the […]

The 75-kD neurotrophin receptor ([p75.sup.NTR]) has been an enigma for a decade. It was among the first growth factor receptors to be cloned (1), but until recently its function remained [...]

A YEAR AGO, NO ONE WOULD HAVE THOUGHT Luis Parada and Moses Chao were chipping away at two sides of the same problem. Chao, a neuroscientist at Cornell University Medical [...]

Expression of Functional Nerve Growth Factor Receptors After Gene Transfer THE MANY PHYSIOLOGICAL EFFECTS of NGF on the survival and maintenance of selective neuronal populations are directly mediated by binding [...]

Expression of the β-Nerve Growth Factor Gene in Hippocampal Neurons NERVE GROWTH FACTOR (NFG) is essential in the development and maintenance of symphathetic and sensory peripheral neurons (1). In central [...]

Nerve Growth Factor Treatment After Brain Injury Prevents Neuronal Death NERVE GROWTH FACTOR (NGF) IScrucial for the normal development and maintenance of peripheral sympathetic and sensory ganglia (1). The administration [...]

Axons in the peripheral nervous system (PNS) of mammals can regenerate after injury, whereas axons in the adult mammalian central nervous system (CNS) typically show only abortive sprouting after lesions [...]

The Neuronal Growth-Associated Protein GAP-43 Induces Filopodia in Non-Neuronal Cells THE PROTEIN GAP-43 IS NEURON-specific and is associated with the membrane of growth cones. Although its specific cellular function is [...]

Neurons have a special communication problem: The length of a nerve cell, from the tip of its axon to its main cell body, can be many centimeters or even a [...]

What Makes Nerves Regenerate? Damage to nerves often results in a permanent loss of function because the tissue fails to regenerate. This is a particular problem in the mammalian spinal [...]

Increased Numbers of Thoracic Dorsal Root Axons in Rats Given Antibodies to Nerve Growth Factor Nerve growth factor (NGF) affects the growth and development of sensory and sympathetic neurons (1, [...]