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

Laboratory of Molecular Neurotherapies and NeuroModulation, Center for Neuroscience Research, Lausanne University Hospital, CHUV-Pavillon 3, av de Beaumont, CH-1010 Lausanne, Switzerland
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J. Clin. Med. 2020, 9(2), 456; https://doi.org/10.3390/jcm9020456
Received: 3 December 2019 / Revised: 31 January 2020 / Accepted: 3 February 2020 / Published: 7 February 2020
(This article belongs to the Special Issue Glial Cells in Central Nervous System (CNS) Pathology and Repair)
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 α1 (GFRα1), 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/GFRα1 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 GFRα1 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 GFRα1 in glial cells, suggesting that GDNF could modulate neuroinflammation. View Full-Text
Keywords: glial-cell-line-derived neurotrophic factor; microglia; astrocyte; neuroinflammation; rearranged during transfection; GDNF family receptor alpha 1; gene therapy; Parkinson’s disease glial-cell-line-derived neurotrophic factor; microglia; astrocyte; neuroinflammation; rearranged during transfection; GDNF family receptor alpha 1; gene therapy; Parkinson’s disease
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MDPI and ACS Style

Duarte Azevedo, M.; Sander, S.; Tenenbaum, L. GDNF, A Neuron-Derived Factor Upregulated in Glial Cells during Disease. J. Clin. Med. 2020, 9, 456. https://doi.org/10.3390/jcm9020456

AMA Style

Duarte Azevedo M, Sander S, Tenenbaum L. GDNF, A Neuron-Derived Factor Upregulated in Glial Cells during Disease. Journal of Clinical Medicine. 2020; 9(2):456. https://doi.org/10.3390/jcm9020456

Chicago/Turabian Style

Duarte Azevedo, Marcelo, Sibilla Sander, and Liliane Tenenbaum. 2020. "GDNF, A Neuron-Derived Factor Upregulated in Glial Cells during Disease" Journal of Clinical Medicine 9, no. 2: 456. https://doi.org/10.3390/jcm9020456

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