関: Glial-cell-derived neurotrophic factor

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/09/20 22:06:30」(JST)

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Glial cell-derived neurotrophic factor, also known as GDNF is a protein that, in humans, is encoded by the GDNF gene.^[1] GDNF is a small protein that potently promotes the survival of many types of neurons.^[2]

Function[edit source | edit]

This gene encodes a highly conserved neurotrophic factor. The recombinant form of this protein was shown to promote the survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons induced by axotomy. The encoded protein is processed to a mature secreted form that exists as a homodimer. The mature form of the protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. In addition to the transcript encoding GDNF, two additional alternative transcripts encoding distinct proteins, referred to as astrocyte-derived trophic factors, have also been described. Mutations in this gene may be associated with Hirschsprung's disease.^[2]

The most prominent feature of GDNF is its ability to support the survival of dopaminergic and motorneurons.

These neuronal populations die in the course of Parkinson's disease and amyotrophic lateral sclerosis (ALS). GDNF also regulates kidney development and spermatogenesis, and it affects alcohol consumption.^[3]

GDNF family of ligands (GFL)[edit source | edit]

GDNF was discovered in 1991,^[4] and is the first member of the GDNF family of ligands (GFL) found.

Interactions[edit source | edit]

Glial cell line-derived neurotrophic factor has been shown to interact with GFRA2^[5]^[6] and GDNF family receptor alpha 1.^[5]^[6]

Potential as therapeutics[edit source | edit]

GDNF has regenerative properties for brain cells and showed potential as treatment for Parkinson's disease - monkeys with an induced form of Parkinson's disease showed less trembling when treated with the drug, and neuronal fibres grew in part of the human brain exposed to the drug.^[4] However progress to a treatment is hampered by the problem of delivering the drug to brain cells through the blood-brain barrier in human.^[4]

References[edit source | edit]

^ Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F (May 1993). "GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons". Science 260 (5111): 1130–2. doi:10.1126/science.8493557. PMID 8493557.
^ ^a ^b "Entrez Gene: GDNF glial cell derived neurotrophic factor".
^ Carnicella S, Kharazia V, Jeanblanc J, Janak PH, Ron D (June 2008). "GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse". Proc. Natl. Acad. Sci. U.S.A. 105 (23): 8114–9. doi:10.1073/pnas.0711755105. PMC 2423415. PMID 18541917.
^ ^a ^b ^c Brian Vastag (2010). "Biotechnology: Crossing the barrier". Nature 466 (7309): 916–8. doi:10.1038/466916a. PMID 20725015.
^ ^a ^b Jing, S; Yu Y, Fang M, Hu Z, Holst P L, Boone T, Delaney J, Schultz H, Zhou R, Fox G M (December 1997). "GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family". J. Biol. Chem. (UNITED STATES) 272 (52): 33111–7. doi:10.1074/jbc.272.52.33111. ISSN 0021-9258. PMID 9407096.
^ ^a ^b Cik, M; Masure S, Lesage A S, Van Der Linden I, Van Gompel P, Pangalos M N, Gordon R D, Leysen J E (September 2000). "Binding of GDNF and neurturin to human GDNF family receptor alpha 1 and 2. Influence of cRET and cooperative interactions". J. Biol. Chem. (UNITED STATES) 275 (36): 27505–12. doi:10.1074/jbc.M000306200. ISSN 0021-9258. PMID 10829012.

External links[edit source | edit]

Glial Cell Line-Derived Neurotrophic Factor at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. パーキンソン病への新たな疾患修飾療法potential disease modifying therapies for parkinson disease [show details]
…disease outside the context of a clinical trial. Direct brain infusion of glial cell line derived neurotrophic factor (GDNF) appeared promising in a phase II open label trial of safety and tolerability …
2. 多発性内分泌腫瘍2型の分類および遺伝学classification and genetics of multiple endocrine neoplasia type 2 [show details]
…binding of one of its four ligands, glial cell line-derived neurotrophic factor (GDNF), neurturin (TNT), artemin, or persephin, which require their specific co-receptors GDNF-receptor-family-a-1 (GFR-a-1), …
3. 筋萎縮性側索硬化症への疾患修飾療法disease modifying treatment of amyotrophic lateral sclerosis [show details]
…postsymptomatic model in the SOD1-mutant mouse model. In a similar method, glial cell line-derived neurotrophic factor (GDNF) gene was injected into lower-extremity muscles of a G93A transgenic mouse using…
4. 先天性巨大結腸症（ヒルシュスプルング病）congenital aganglionic megacolon hirschsprung disease [show details]
…including those derived from the neural crest. Glial cell line-derived neurotrophic factor (GDNF) and neurturin have been identified as ligands for RET, and GDNF, which is essential for normal enteric nervous …
5. 気道の神経制御neuronal control of the airways [show details]
…glial cell-derived neurotrophic factor (GDNF)-family ligands including GDNF, artemin, neurturin, and persephin . These ligands bind with high affinity to receptors; GDNF to GFR-alpha1, neurturin to GFR-alpha2 …

English Journal

Mitigation of cerebellar neuropathy in globoid cell leukodystrophy mice by AAV-mediated gene therapy.

Lin DS1, Hsiao CD2, Lee AY3, Ho CS4, Liu HL5, Wang TJ6, Jian YR7, Hsu JC7, Huang ZD7, Lee TH7, Chiang MF8.
Gene.Gene.2015 Oct 15;571(1):81-90. doi: 10.1016/j.gene.2015.06.049. Epub 2015 Jun 23.
Globoid cell leukodystrophy (GLD) is an autosomal recessive, lysosomal storage disease caused by deficiency of the enzyme galactocerebrosidase (GALC). The absence of GALC activity leads to the accumulation of the toxic substance psychosine and the preferential loss of myelinating cells in the centra
PMID 26115766

GDNF-secreting mesenchymal stem cells provide localized neuroprotection in an inflammation-driven rat model of Parkinson's disease.

Hoban DB1, Howard L2, Dowd E3.
Neuroscience.Neuroscience.2015 Sep 10;303:402-11. doi: 10.1016/j.neuroscience.2015.07.014. Epub 2015 Jul 10.
Constraints involving the delivery method of glial cell line-derived neurotrophic factor (GDNF) have hampered its efficacy as a neuroprotectant in Parkinson's disease. Ex vivo gene therapy, in which suitable cells, such as bone marrow-derived mesenchymal stem cells (MSCs), are genetically engineered
PMID 26166730

Intranasal administration of glial-derived neurotrophic factor (GDNF) rapidly and significantly increases whole-brain GDNF level in rats.

Bender TS1, Migliore MM2, Campbell RB3, John Gatley S1, Waszczak BL4.
Neuroscience.Neuroscience.2015 Sep 10;303:569-76. doi: 10.1016/j.neuroscience.2015.07.016. Epub 2015 Jul 9.
Previous studies have shown that glial cell line-derived neurotrophic factor (GDNF) exerts significant neuroprotective effects on substantia nigra (SN) neurons in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD). In this study we used enzyme-linked immunosorbent assay (ELISA) to
PMID 26166725

Japanese Journal

Functional Differences between GDNF-Dependent and FGF2-Dependent Mouse Spermatogonial Stem Cell Self-Renewal

Takashima Seiji,Kanatsu-Shinohara Mito,Tanaka Takashi,Morimoto Hiroko,Inoue Kimiko,Ogonuki Narumi,Jijiwa Mayumi,Takahashi Masahide,Ogura Atsuo,Shinohara Takashi
Stem Cell Reports 4(3), 489-502, 2015-02
… Earlier studies showed that glial cell line-derived neurotrophic factor (GDNF) was indispensable for SSC self-renewal by binding to the GFRA1/RET receptor. … Here we show that SSCs undergo GDNF-independent self-renewal. … Moreover, fibroblast growth factor 2 (FGF2) supplementation enabled in vitro SSC expansion without GDNF. … Although GDNF-mediated self-renewal signaling required both AKT and MAP2K1/2, the latter was dispensable in FGF2-mediated self-renewal. …
NAID 120005540400

Hypoxia-inducible factor 1 alpha regulates branching morphogenesis during kidney development

Tsuji Kenji,Kitamura Shinji,Makino Hirofumi
Biochemical and Biophysical Research Communications 447(1), 108-114, 2014-04-25
… In addition, the mRNA levels of GDNF and GDNF receptor (GFR-alpha l), increased under hypoxic conditions in E13K5. … In addition, the expression of GDNF and GFR-alpha 1 was inhibited under hypoxic conditions when the kidneys were treated with siRNA targeting HIF-1 alpha. … Hypoxia might mediate branching morphogenesis via not only GDNF/Ret but also FGF signaling pathway. …
NAID 120005526618

血液神経関門と糖尿病性ニューロパチー : 糖尿病性ニューロパチーでは血液神経関門が破綻する(ミニ・レビュー : 中村賞受賞者)

清水文崇
山口医学 63(1), 17-24, 2014-02-01
… ,われわれはヒト坐骨神経よりBNB由来の血管内皮細胞とペリサイトの不死化細胞株を作製し,世界に先駆けてヒトBNB in vitroモデルを樹立した.このBNB in vitroモデルを用いて,われわれはペリサイトが分泌するbFGFとGDNFがBNB機能を高めることを明らかとし,BNBではペリサイトがバリアー機能を制御する主要なレギュレーターであることを示した.さらに,糖尿病性ニューロパチーでは形態学的にBNBが局在する微小血管の基底膜肥厚 …
NAID 120005435142

Related Pictures

Novel functions and signalling pathways for GDNF | Journal of Cell Science Frontiers | GDNF-based therapies, GDNF-producing interneurons, and trophic support of Neuropeptide Y functions as a facilitator of GDNF-induced budding of the Wolffian duct File:GDNF.jpg - Wikimedia Commons Catecholaminergic neuron survival: getting hooked on GDNF | Nature Neuroscience GDNF, an important regulator of dopamine neurons in the brain – Science Mission QIAGEN - GeneGlobe Pathways - GDNF-Family Ligands and Receptor Interactions

★リンクテーブル★

リンク元	「グリア細胞由来神経栄養因子」「glial cell line-derived neurotrophic factor」
拡張検索	「GDNF receptor」「GDNF受容体」「GDNFレセプター」

「グリア細胞由来神経栄養因子」

Glial cell derived neurotrophic factor
	; GDNF structure
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	2V5E, 3FUB
Identifiers
Symbols	GDNF; ATF1; ATF2; HFB1-GDNF; HSCR3
External IDs	OMIM: 600837 MGI: 107430 HomoloGene: 433 GeneCards: GDNF Gene
Gene Ontology
Molecular function	• receptor binding; • growth factor activity; • protein homodimerization activity;
Cellular component	• extracellular region;
Biological process	• metanephros development; • branching involved in ureteric bud morphogenesis; • neural crest cell migration; • organ induction; • postsynaptic membrane organization; • mesenchymal to epithelial transition involved in metanephros morphogenesis; • signal transduction; • nervous system development; • axon guidance; • adult locomotory behavior; • postganglionic parasympathetic nervous system development; • peristalsis; • neuron projection development; • positive regulation of monooxygenase activity; • positive regulation of dopamine secretion; • negative regulation of apoptotic process; • negative regulation of neuron apoptotic process; • positive regulation of transcription from RNA polymerase II promoter; • mRNA stabilization; • enteric nervous system development; • sympathetic nervous system development; • regulation of dopamine uptake involved in synaptic transmission; • ureteric bud formation; • regulation of morphogenesis of a branching structure; • positive regulation of ureteric bud formation; • positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis; • positive regulation of branching involved in ureteric bud morphogenesis; • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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