The reversible effects of glial cell line–derived neurotrophic factor (GDNF) in the human brain

Abstract

Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor, and a member of the transforming growth factor β (TGF-β) superfamily acting on different neuronal activities. GDNF was originally identified as a neurotrophic factor crucially involved in the survival of dopaminergic neurons of the nigrostriatal pathway and is currently an established therapeutic target in Parkinson's disease. However, GDNF was later reported to be highly expressed in gliomas, especially in glioblastomas, and was demonstrated as a potent proliferation factor involved in the development and migration of gliomas. Here, we review our current understanding and progress made so far by researchers in our laboratories with references to relevant articles to support our discoveries. We present past and recent discoveries on the mechanisms involved in the protection of neurons by GDNF and examine its emerging roles in gliomas, as well as reasons for the abnormal expression in Glioblastoma Multiforme (GBM). Collectively, our work establishes a paradigm by which the ability of GDNF to protect dopaminergic neurons from degradation and its corresponding effects on glioma cells points to an underlying biological vulnerability in the effects of GDNF in the normal brain which can be subverted for use by cancer cells. Hence, presenting novel opportunities for intervention in glioma therapies.

Neuro-regenerative imidazole-functionalized GelMA hydrogel loaded with hAMSC and SDF-1α promote stem cell differentiation and repair focal brain injury

“…Glial cell line-derived neurotrophic factor (GDNF) is crucially important for the development and maintenance of brain tissue. As an important neuroprotective therapeutic candidate, it has been widely used to treat Parkinson's disease [ 37 ]. The H&E staining results indicated that the GelMA-imid/SDF-1α/hAMSC hydrogel could significantly promote the proliferation of glial cells in the early stage of injury, which might produce GDNF to maintain and regenerate brain tissue.…”

<p>Astroglial Mechanisms Underlying Chronic Insomnia Disorder: A Clinical Study</p>

“…It has been implicated in neuropsychiatric disorders, neurodegenerative diseases, brain injury and neuroinflammation. 51 – 53 Abbreviations: S100B, S100 calcium binding protein B; GFAP, glial fibrillary acidic protein; BDNF, brain derived neurotrophic factor; GDNF, glial derived neurotrophic factor; CNS, central nervous system. …”

“…The reason may be that astrocytes are actively involved in normal memory functions and in the abnormal processes, including astroglial injury, leading to cognitive impairment in pathological conditions. 53 Even a few hours of sleep deprivation led to astrocytic processes extending closer to the synaptic cleft. These structural changes potentially represent the importance of positioning astrocytes adjacent to synapses for the clearance of neurotransmitters via astrocytic transporters or for the transmission of glial-derived signals to support synaptic plasticity.…”

Pandemrix-induced narcolepsy is associated with genes related to immunity and neuronal survival

“…The exon 4 variant rs75921262 also has annotations suggesting a gene regulatory effect on GDNF in skeletal muscle and skin. The neurotrophic factor GDNF is, however, predominantly produced by multiple cell types in the central and peripheral nervous system, and has a beneficial effect on several cells including sympathetic, parasympathetic, sensory, and motor neurons [26,27]. Neurotrophic factors have been demonstrated to activate neuronal repair genes under conditions of neurodegeneration [28].…”