GDNF, A Neuron-Derived Factor Upregulated in Glial Cells during Disease

被引:90
作者
Azevedo, Marcelo Duarte [1 ]
Sander, Sibilla [1 ]
Tenenbaum, Liliane [1 ]
机构
[1] Lausanne Univ Hosp, Ctr Neurosci Res, Lab Mol Neurotherapies & NeuroModulat, CHUV Pavillon 3,Av Beaumont, CH-1010 Lausanne, Switzerland
基金
瑞士国家科学基金会;
关键词
glial-cell-line-derived neurotrophic factor; microglia; astrocyte; neuroinflammation; rearranged during transfection; GDNF family receptor alpha 1; gene therapy; Parkinson's disease; NEUROTROPHIC FACTOR GDNF; TRANSGENIC MOUSE MODEL; REACTIVE ASTROCYTES; MESSENGER-RNA; GENE-THERAPY; LONG-TERM; C-RET; DESTABILIZING DOMAINS; NORADRENERGIC NEURONS; TYROSINE-HYDROXYLASE;
D O I
10.3390/jcm9020456
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In a healthy adult brain, glial cell line-derived neurotrophic factor (GDNF) is exclusively expressed by neurons, and, in some instances, it has also been shown to derive from a single neuronal subpopulation. Secreted GDNF acts in a paracrine fashion by forming a complex with the GDNF family receptor alpha 1 (GFR alpha 1), which is mainly expressed by neurons and can act in cis as a membrane-bound factor or in trans as a soluble factor. The GDNF/GFR alpha 1 complex signals through interactions with the "rearranged during transfection" (RET) receptor or via the neural cell adhesion molecule (NCAM) with a lower affinity. GDNF can also signal independently from GFR alpha 1 by interacting with syndecan-3. RET, which is expressed by neurons involved in several pathways (nigro-striatal dopaminergic neurons, motor neurons, enteric neurons, sensory neurons, etc.), could be the main determinant of the specificity of GDNF's pro-survival effect. In an injured brain, de novo expression of GDNF occurs in glial cells. Neuroinflammation has been reported to induce GDNF expression in activated astrocytes and microglia, infiltrating macrophages, nestin-positive reactive astrocytes, and neuron/glia (NG2) positive microglia-like cells. This disease-related GDNF overexpression can be either beneficial or detrimental depending on the localization in the brain and the level and duration of glial cell activation. Some reports also describe the upregulation of RET and GFR alpha 1 in glial cells, suggesting that GDNF could modulate neuroinflammation.
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页数:13
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共 101 条
[1]   Glial cell line-derived neurotrophic factor is expressed by inflammatory cells in the sciatic nerves of Lewis rats with experimental autoimmune neuritis [J].
Ahn, Meejung ;
Jin, Jae-Kwang ;
Moon, Changjong ;
Matsumoto, Yoh ;
Koh, Chang-Sung ;
Shin, Taekyun .
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, 2010, 15 (02) :104-112
[2]   GDNF family neurotrophic factor signaling: Four masters, one servant? [J].
Airaksinen, MS ;
Titievsky, A ;
Saarma, M .
MOLECULAR AND CELLULAR NEUROSCIENCE, 1999, 13 (05) :313-325
[3]   GDNF prevents degeneration and promotes the phenotype of brain noradrenergic neurons in vivo [J].
Arenas, E ;
Trupp, M ;
Akerud, P ;
Ibanez, CF .
NEURON, 1995, 15 (06) :1465-1473
[4]   Characterization of a promoter for the human glial cell line-derived neurotrophic factor gene [J].
Baecker, PA ;
Lee, WH ;
Verity, AN ;
Eglen, RM ;
Johnson, RM .
MOLECULAR BRAIN RESEARCH, 1999, 69 (02) :209-222
[5]   Post-mortem assessment of the short and long-term effects of the trophic factor neurturin in patients with α-synucleinopathies [J].
Bartus, R. T. ;
Kordower, J. H. ;
Johnson, E. M., Jr. ;
Brown, L. ;
Kruegel, B. R. ;
Chu, Y. ;
Baumann, T. L. ;
Lang, A. E. ;
Olanow, C. W. ;
Herzog, C. D. .
NEUROBIOLOGY OF DISEASE, 2015, 78 :162-171
[6]   Bioactivity of AAV2-Neurturin Gene Therapy (CERE-120): Differences Between Parkinson's Disease and Nonhuman Primate Brains [J].
Bartus, Raymond T. ;
Herzog, Christopher D. ;
Chu, Yaping ;
Wilson, Alistair ;
Brown, Lamar ;
Siffert, Joao ;
Johnson, Eugene M., Jr. ;
Olanow, C. Warren ;
Mufson, Elliott J. ;
Kordower, Jeffrey H. .
MOVEMENT DISORDERS, 2011, 26 (01) :27-36
[7]   Inhibition of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression reduces dopaminergic sprouting in the injured striatum [J].
Batchelor, PE ;
Liberatore, GT ;
Porritt, MJ ;
Donnan, GA ;
Howells, DW .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2000, 12 (10) :3462-3468
[8]   Macrophages and microglia produce local trophic gradients that stimulate axonal sprouting toward but not beyond the wound edge [J].
Batchelor, PE ;
Porritt, MJ ;
Martinello, P ;
Parish, CL ;
Liberatore, GT ;
Donnan, GA ;
Howells, DW .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2002, 21 (03) :436-453
[9]  
Batchelor PE, 1999, J NEUROSCI, V19, P1708
[10]   Heparan sulfate proteoglycan syndecan-3 is a novel receptor for GDNF, neurturin, and artemin [J].
Bespalov, Maxim M. ;
Sidorova, Yulia A. ;
Tumova, Sarka ;
Ahonen-Bishopp, Anni ;
Magalhaes, Ana Cathia ;
Kulesskiy, Evgeny ;
Paveliev, Mikhail ;
Rivera, Claudio ;
Rauvala, Heikki ;
Saarma, Mart .
JOURNAL OF CELL BIOLOGY, 2011, 192 (01) :153-169