GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther

Dorothy Hodgkin Building, Whitson St, Bristol BS1 3NY UK. Electronic address: .
Pharmacology [?] Therapeutics (Impact Factor: 9.72). 01/2013; 138(2). DOI: 10.1016/j.pharmthera.2013.01.004
Source: PubMed


Glial cell-derived neurotrophic factor (GDNF), and the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are important for the survival, maintenance and regeneration of specific neuronal populations in the adult brain. Depletion of these neurotrophic factors has been linked with disease pathology and symptoms, and replacement strategies are considered as potential therapeutics for neurodegenerative diseases such as Parkinson's, Alzheimer's and Huntington's disease. GDNF administration has recently been shown to be an effective treatment for Parkinson's disease, with clinical trials currently in progress. Trials with NGF for Alzheimer's disease are ongoing, with some degree of success. Preclinical results using BDNF also show much promise, although there are accompanying difficulties. Ultimately, the administration of a therapy involving proteins in the brain has inherent problems. Because of the blood-brain-barrier, the protein must be infused directly, produced by viral constructs, secreted from implanted protein-secreting cells or actively transported across into the brain. An alternative to this is the use of a small molecule agonist, a modulator or enhancer targeting the associated receptors. We evaluate these neurotrophic factors as potential short or long-term treatments, weighing up preclinical and clinical results with the possible effects on the underlying neurodegenerative process.

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    • "Studies on the use of various growth factors to promote peripheral nerve regeneration have gradually increased (Table 2), with an improved understanding of neurotrophic components that are released from nerve endings and their effect on nerve growth and differentiation. These neurotrophic factors, expressed at different intervals during nerve regeneration to accelerate axonal growth, include nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and insulinlike growth factor-1 (IGF-1), all of which are secreted from Schwann cells[29]. Fibroblast growth factors (FGFs) have a significant role in cell growth and regeneration and are released from damaged nerve ending[30]. Subsequent studies have worked on combining FGF with structural components. "
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    • "Previous reports have suggested that in addition to cytokines, nitric oxide (NO) and neurotrophic factors, such as brain derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF) and nerve growth factor (NGF), might also contribute to the pathogenesis of CM (Gazzinelli et al., 2014; Jeney et al., 2014; Linares et al., 2013). Neurotrophic factors are a large group of growth factors essential for physiological functioning and the development of the nervous system (Allen et al., 2013). BDNF levels are reduced in the brains of humans with neurodegenerative diseases, such as Alzheimer disease (Zuccato and Cattaneo, 2009). "
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