Persephin
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Persephin
Persephin is a neurotrophic factor in the glial cell line-derived neurotrophic factor (GDNF) family. Persephin shares around a 40% similarity in amino acid sequence compared to GDNF and neurturin, two members of the GDNF family. Function Persephin has been found to be less potent than other members of the GDNF family of ligands, GDNF family. It has been found to support the survival and morphological differentiation of tyrosine hydroxylase immunoreactive neurons, although less so than both GDNF and neurturin. The mRNA levels of persephin in developing neurons has been low compared to other neurotrophic factors, but relatively higher levels of persephin mRNA have been found in embryonic neurons. Similarly to the other members of the GDNF family of ligands, persephin uses a receptor that consists of the tyrosine kinase signaling component Ret and a unit of glycosylphosphatidylinsitol (GPI)-anchored receptor (GFRα). Persephin specifically binds to GFRα4. Persephin acts on both ...
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Neurotrophic Factor
Neurotrophic factors (NTFs) are a family of biomolecules – nearly all of which are peptides or small proteins – that support the growth, survival, and cell differentiation, differentiation of both developing and mature neurons. Most NTFs exert their trophic effects on neurons by signaling through tyrosine kinases, usually a receptor tyrosine kinase. In the mature nervous system, they promote neuronal survival, induce synaptic plasticity, and modulate the formation of long-term memories. Neurotrophic factors also promote the initial growth and development of neurons in the central nervous system and peripheral nervous system, and they are capable of regrowing damaged neurons in test tubes and animal models. Some neurotrophic factors are also released by the target tissue in order to axon guidance, guide the growth of developing axons. Most neurotrophic factors belong to one of three families: (1) neurotrophins, (2) glial cell-line derived neurotrophic factor family liga ...
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GDNF Family Of Ligands
The GDNF family of ligands (GFL) consists of four neurotrophic factors: glial cell line-derived neurotrophic factor (GDNF), neurturin (NRTN), artemin (ARTN), and persephin (PSPN). GFLs have been shown to play a role in a number of biological processes including cell survival, neurite outgrowth, cell differentiation and cell migration. In particular signalling by GDNF promotes the survival of dopaminergic neurons. Signalling complex formation At the cell surface of target cells, a signalling complex forms, composed of a particular GFL dimer, a receptor tyrosine kinase molecule RET, and a cell surface-bound co-receptor that is a member of the GFRα protein family. The primary ligands for the co-receptors GFRα1, GFRα2, GFRα3, and GFRα4 are GDNF, NRTN, ARTN, and PSPN, respectively. Upon initial GFL-GFRα complex formation, the complex then brings together two molecules of RET, triggering trans-autophosphorylation of specific tyrosine residues within the tyrosine kinase domain o ...
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GDNF Family Ligands
The GDNF family of ligands (GFL) consists of four neurotrophic factors: glial cell line-derived neurotrophic factor (GDNF), neurturin (NRTN), artemin (ARTN), and persephin (PSPN). GFLs have been shown to play a role in a number of biological processes including cell survival, neurite outgrowth, cell differentiation and cell migration. In particular signalling by GDNF promotes the survival of dopaminergic neurons. Signalling complex formation At the cell surface of target cells, a signalling complex forms, composed of a particular GFL dimer, a receptor tyrosine kinase molecule RET, and a cell surface-bound co-receptor that is a member of the GFRα protein family. The primary ligands for the co-receptors GFRα1, GFRα2, GFRα3, and GFRα4 are GDNF, NRTN, ARTN, and PSPN, respectively. Upon initial GFL-GFRα complex formation, the complex then brings together two molecules of RET, triggering trans-autophosphorylation of specific tyrosine residues within the tyrosine kinase domain of ...
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Glial Cell Line-derived Neurotrophic Factor
Glial cell line-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the ''GDNF'' gene. GDNF is a small protein that potently promotes the survival of many types of neurons. It signals through GFRα receptors, particularly GFRα1. It is also responsible for the determination of spermatogonia into primary spermatocytes, i.e. it is received by RET proto-oncogene (RET) and by forming gradient with SCF it divides the spermatogonia into two cells. As the result there is retention of spermatogonia and formation of spermatocyte. GDNF family of ligands (GFL) GDNF was discovered in 1991, and is the first member of the GDNF family of ligands (GFL) found. Function GDNF is highly distributed throughout both the peripheral and central nervous system. It can be secreted by astrocytes, oligodendrocytes, Schwann cells, motor neurons, and skeletal muscle during the development and growth of neurons and other peripheral cells. The GDNF gene encodes a highly conserved ...
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GDNF
Glial cell line-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the ''GDNF'' gene. GDNF is a small protein that potently promotes the survival of many types of neurons. It signals through GFRα receptors, particularly GFRα1. It is also responsible for the determination of spermatogonia into primary spermatocytes, i.e. it is received by RET proto-oncogene (RET) and by forming gradient with SCF it divides the spermatogonia into two cells. As the result there is retention of spermatogonia and formation of spermatocyte. GDNF family of ligands (GFL) GDNF was discovered in 1991, and is the first member of the GDNF family of ligands (GFL) found. Function GDNF is highly distributed throughout both the peripheral and central nervous system. It can be secreted by astrocytes, oligodendrocytes, Schwann cells, motor neurons, and skeletal muscle during the development and growth of neurons and other peripheral cells. The GDNF gene encodes a highly conserved ...
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Neurturin
Neurturin (NRTN) is a protein that is encoded in humans by the ''NRTN'' gene. Neurturin belongs to the glial cell line-derived neurotrophic factor (GDNF) family of neurotrophic factors, which regulate the survival and function of neurons. Neurturin’s role as a growth factor places it in the transforming growth factor beta (TGF-beta) subfamily along with its homologs persephin, artemin, and GDNF. It shares a 42% similarity in amino acid sequence with mature GDNF. It is also considered a trophic factor and critical in the development and growth of neurons in the brain. Neurotrophic factors like neurturin have been tested in several clinical trial settings for the potential treatment of neurodegenerative diseases, specifically Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor ...
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Ramogen
The term ramogen refers to a biological factor, typically a growth factor or other protein, that causes a developing biological cell or tissue to branch in a tree-like manner. Ramogenic molecules are branch promoting molecules found throughout the human body,. Brief History The term was first coined (from the Latin ramus = branch and the Greek genesis = creation) in an article about kidney development by Davies and Davey (Pediatr Nephrol. 1999 Aug;13(6):535-41). In the article, Davies and Davy describe the existence of "ramogens" in the kidney as glial cell line-derived neurotrophic factors, neurturin and persephin. The term has now passed into general use in the technical literature concerned with branching of biological structures. Function A ramogen is a biochemical signal that enables the creation of a physiological branch. The signal can be in the form of a growth factor or a hormone that makes a tube branch. One specific example would be the hormone that forms the simple ...
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Parkinson's Disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms become more common. The most obvious early symptoms are tremor, rigidity, slowness of movement, and difficulty with walking. Cognitive and behavioral problems may also occur with depression, anxiety, and apathy occurring in many people with PD. Parkinson's disease dementia becomes common in the advanced stages of the disease. Those with Parkinson's can also have problems with their sleep and sensory systems. The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain, leading to a dopamine deficit. The cause of this cell death is poorly understood, but involves the build-up of misfolded proteins into Lewy bodies in the neurons. Collectively, the main motor symptoms are also known as ...
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Motor Neurons
A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectly control effector organs, mainly muscles and glands. There are two types of motor neuron – upper motor neurons and lower motor neurons. Axons from upper motor neurons synapse onto interneurons in the spinal cord and occasionally directly onto lower motor neurons. The axons from the lower motor neurons are efferent nerve fibers that carry signals from the spinal cord to the effectors. Types of lower motor neurons are alpha motor neurons, beta motor neurons, and gamma motor neurons. A single motor neuron may innervate many muscle fibres and a muscle fibre can undergo many action potentials in the time taken for a single muscle twitch. Innervation takes place at a neuromuscular junction and twitches can become superimposed as a result of ...
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TGFβ Domain
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other signaling proteins. TGFB proteins are produced by all white blood cell lineages. Activated TGF-β complexes with other factors to form a serine/threonine kinase complex that binds to TGF-β receptors. TGF-β receptors are composed of both type 1 and type 2 receptor subunits. After the binding of TGF-β, the type 2 receptor kinase phosphorylates and activates the type 1 receptor kinase that activates a signaling cascade. This leads to the activation of different downstream substrates and regulatory proteins, inducing transcription of different target genes that function in differentiation, chemotaxis, proliferation, and activation of many immune cells. TGF-β is secreted by many cell types, including macrophages, in a latent form in which it ...
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