GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson's disease

Frontiers in Neuroanatomy
Xavier d'Anglemont de TassignyJosé López-Barneo

Abstract

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 (PV+) GABAergic interneurons is responsible for most of the GDNF produced in the rodent striatum. In addition, cholinergic striatal interneurons appear to...Continue Reading

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Citations

Feb 6, 2016·International Journal of Molecular Sciences·Bhairavi SrinageshwarJulien Rossignol
Oct 7, 2015·Frontiers in Neuroanatomy·Javier BlesaJose A Obeso
Jul 26, 2016·Frontiers in Neuroanatomy·Clara Ortega-de San Luis, Alberto Pascual
Jan 14, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Daniel Enterría-MoralesXavier d'Anglemont de Tassigny
Feb 26, 2019·Frontiers in Neuroscience·Sumonto MitraMaria Eriksdotter
Dec 11, 2020·Cellular and Molecular Neurobiology·Mayukha BathiniKrishna Kishore Mahato
Dec 11, 2020·Cells·Ikuko Miyazaki, Masato Asanuma
Oct 9, 2021·Essays in Biochemistry·Stefano EspinozaStefano Gustincich

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Methods Mentioned

BETA
transfection
enzyme-linked immunosorbant assay
acetylation
ELISA

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