GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson’s disease
The glial cell line-derived neurotrophic factor (GDNF) is a well-established trophic agent for dopaminergic (DA) neurons in vitro and in vivo. GDNF is necessary for maintenance of neuronal morphological and neurochemical phenotype and protects DA neurons from toxic damage. Numerous studies on animal...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-02-01
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| Series: | Frontiers in Neuroanatomy |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnana.2015.00010/full |
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| author | Xavier ed'Anglemont De Tassigny Xavier ed'Anglemont De Tassigny Alberto ePascual Alberto ePascual Alberto ePascual Jose eLopez-Barneo Jose eLopez-Barneo Jose eLopez-Barneo |
| author_facet | Xavier ed'Anglemont De Tassigny Xavier ed'Anglemont De Tassigny Alberto ePascual Alberto ePascual Alberto ePascual Jose eLopez-Barneo Jose eLopez-Barneo Jose eLopez-Barneo |
| author_sort | Xavier ed'Anglemont De Tassigny |
| collection | DOAJ |
| description | The glial cell line-derived neurotrophic factor (GDNF) is a well-established trophic agent for dopaminergic (DA) neurons in vitro and in vivo. GDNF is necessary for maintenance of neuronal morphological and neurochemical phenotype and protects DA neurons from toxic damage. Numerous studies on animal models of Parkinson’s disease (PD) have reported beneficial effects of GDNF on nigrostriatal DA neuron survival. However, translation of these observations to the clinical setting has been hampered so far by side effects associated with the chronic continuous intra-striatal infusion of recombinant GDNF. In addition, double blind and placebo-controlled clinical trials have not reported any clinically relevant effect of GDNF on PD patients. In the past few years, experiments with conditional Gdnf knockout mice have suggested that GDNF is necessary for maintenance of DA neurons in adulthood. In parallel, new methodologies for exogenous GDNF delivery have been developed. Recently, it has been shown that a small population of scattered, electrically interconnected, parvalbumin positive GABAergic interneurons is responsible for most of the GDNF produced in the rodent striatum. In addition, cholinergic striatal interneurons appear to be also involved in the modulation of striatal GDNF. In this review, we summarize current knowledge on brain GDNF delivery, homeostasis, and its effects on nigrostriatal DA neurons. Special attention is paid to the therapeutic potential of endogenous GDNF stimulation in PD. |
| first_indexed | 2024-04-13T01:49:53Z |
| format | Article |
| id | doaj.art-c6a0ddad6b744c86a1b74079e931c033 |
| institution | Directory Open Access Journal |
| issn | 1662-5129 |
| language | English |
| last_indexed | 2024-04-13T01:49:53Z |
| publishDate | 2015-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroanatomy |
| spelling | doaj.art-c6a0ddad6b744c86a1b74079e931c0332022-12-22T03:07:54ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292015-02-01910.3389/fnana.2015.00010126738GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson’s diseaseXavier ed'Anglemont De Tassigny0Xavier ed'Anglemont De Tassigny1Alberto ePascual2Alberto ePascual3Alberto ePascual4Jose eLopez-Barneo5Jose eLopez-Barneo6Jose eLopez-Barneo7Instituto de Biomedicina de Sevilla (IBiS)Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)Instituto de Biomedicina de Sevilla (IBiS)Consejo Superior de Investigaciones Científicas (CSIC)Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)Instituto de Biomedicina de Sevilla (IBiS)Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)Universidad de Sevilla Departamento de Fisiología Médica y Biofísica, Facultad de Medicina,The glial cell line-derived neurotrophic factor (GDNF) is a well-established trophic agent for dopaminergic (DA) neurons in vitro and in vivo. GDNF is necessary for maintenance of neuronal morphological and neurochemical phenotype and protects DA neurons from toxic damage. Numerous studies on animal models of Parkinson’s disease (PD) have reported beneficial effects of GDNF on nigrostriatal DA neuron survival. However, translation of these observations to the clinical setting has been hampered so far by side effects associated with the chronic continuous intra-striatal infusion of recombinant GDNF. In addition, double blind and placebo-controlled clinical trials have not reported any clinically relevant effect of GDNF on PD patients. In the past few years, experiments with conditional Gdnf knockout mice have suggested that GDNF is necessary for maintenance of DA neurons in adulthood. In parallel, new methodologies for exogenous GDNF delivery have been developed. Recently, it has been shown that a small population of scattered, electrically interconnected, parvalbumin positive GABAergic interneurons is responsible for most of the GDNF produced in the rodent striatum. In addition, cholinergic striatal interneurons appear to be also involved in the modulation of striatal GDNF. In this review, we summarize current knowledge on brain GDNF delivery, homeostasis, and its effects on nigrostriatal DA neurons. Special attention is paid to the therapeutic potential of endogenous GDNF stimulation in PD.http://journal.frontiersin.org/Journal/10.3389/fnana.2015.00010/fullParkinson DiseaseStriatummouse modelsdopaminergic systemneurotrophic factorsNigrostriatal pathway |
| spellingShingle | Xavier ed'Anglemont De Tassigny Xavier ed'Anglemont De Tassigny Alberto ePascual Alberto ePascual Alberto ePascual Jose eLopez-Barneo Jose eLopez-Barneo Jose eLopez-Barneo GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson’s disease Frontiers in Neuroanatomy Parkinson Disease Striatum mouse models dopaminergic system neurotrophic factors Nigrostriatal pathway |
| title | GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson’s disease |
| title_full | GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson’s disease |
| title_fullStr | GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson’s disease |
| title_full_unstemmed | GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson’s disease |
| title_short | GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson’s disease |
| title_sort | gdnf based therapies gdnf producing interneurons and trophic support of the dopaminergic nigrostriatal pathway implications for parkinson s disease |
| topic | Parkinson Disease Striatum mouse models dopaminergic system neurotrophic factors Nigrostriatal pathway |
| url | http://journal.frontiersin.org/Journal/10.3389/fnana.2015.00010/full |
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