Since its discovery almost three decades ago, the secreted neurotrophin brain-derived neurotrophic factor (BDNF) has been firmly implicated in the differentiation and survival of neurons of the CNS. More recently, BDNF has also emerged as an important regulator of synaptogenesis and synaptic plasticity mechanisms underlying learning and memory in the adult CNS. In this review we will discuss ou...

Morphogenesis during development is fundamental to the differentiation of several cell types. As neurite outgrowth marks neuritogenesis, formation of filopodia precede the formation of dendrites and axons. While the structure of filopodia is well-known, the initiation of filopodia during neurite outgrowth is not clear. SH2B1 is known to promote neurite outgrowth of PC12 cells, hippocampal and c...

Neurotrophins regulate cell survival, death, differentiation and growth. Neurotrophins and their receptors have been validated for pathologies including neurodegenerative disorders of the central nervous system and the peripheral nervous system, certain types of cancers, asthma, inflammation and others. Development of neurotrophin-based therapeutics is important due to the limitations of using ...

During the formation of neuronal circuits, neurons respond to diffusible cues secreted by target tissues. Often, target-derived signals act on nerve terminals to influence local growth events; in other cases, they are transported long distances back to neuronal cell bodies to effect transcriptional changes necessary for neuronal survival and differentiation. Neurotrophins provide one of the bes...

A proteolytically stable small molecule beta-turn peptidomimetic, termed D3, was identified as an agonist of the TrkA neurotrophin receptor. D3 binds the Ig-like C2 region of the extracellular domain of TrkA, competes the binding of another TrkA agonist, affords selective trophic protection to TrkA-expressing cell lines and neuronal primary cultures, and induces the differentiation of primary n...

The expression pattern of Necdin, a gene involved in the etiology of Prader-Willi syndrome and a member of the MAGE family of genes, is described during mouse nervous system development. Using RNA in situ hybridization, immunohistochemical staining, and colocalization with neuronal differentiation markers, we found that Necdin RNA and protein are expressed within post-mitotic neurons at all sta...

The 14-3-3 proteins exist predominantly in the brain and may play regulatory roles in cellular processes of growth, differentiation, survival, and apoptosis. The biological functions, however, of the various 14-3-3 isoforms (beta, epsilon, eta, gamma, and zeta) in the brain remain unclear. We have reported previously upregulation of 14-3-3gamma in ischemic astrocytes. In the present study, we r...

Neurotrophins influence the epigenetic shaping of the vertebrate nervous system by regulating neuronal numbers during development and synaptic plasticity. Here we attempt to determine whether these growth factors can also regulate neurotransmitter plasticity. As a model system we used the selection between noradrenergic and cholinergic neurotransmission by paravertebral sympathetic neurons. Dev...

hippocampal neural stem/progenitor cells (hipp-ns/pcs) of the adult mammalian brain are important sources of neuronal and gial cell production. in this study, the main goal is to investigate the plasticity of these cells in neuronal/astroglial differentiations. to this end, the differentiation of the hipp-ns/pcs isolated from 3-month-old wistar rats was investigated in response to the embryonic...

Neurotrophin receptor tyrosine kinases (Trks) have well-defined trophic roles in nervous system development through kinase activation by neurotrophins. Yet Trks have typical cell-adhesion domains and express noncatalytic isoforms, suggesting additional functions. Here we discovered noncatalytic TrkC in an unbiased hippocampal neuron-fibroblast coculture screen for proteins that trigger differen...