GDNF, NGF and BDNF as therapeutic options for neurodegeneration

• Published in: Pharmacology & therapeutics (Oxford) Vol. 138; no. 2; pp. 155 - 175
• Main Authors: ALLEN, Shelley J, WATSON, Judy J, SHOEMARK, Deborah K, BARUA, Neil U, PATEL, Nikunj K
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 01.05.2013
• Subjects: Adult and adolescent clinical studies; Animals; Biological and medical sciences; Brain-Derived Neurotrophic Factor - administration & dosage; Brain-Derived Neurotrophic Factor - chemistry; Brain-Derived Neurotrophic Factor - metabolism; Brain-Derived Neurotrophic Factor - therapeutic use; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Glial Cell Line-Derived Neurotrophic Factor - administration & dosage; Glial Cell Line-Derived Neurotrophic Factor - chemistry; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Glial Cell Line-Derived Neurotrophic Factor - therapeutic use; Humans; Ligands; Medical sciences; Models, Molecular; Nerve Growth Factors - administration & dosage; Nerve Growth Factors - chemistry; Nerve Growth Factors - metabolism; Nerve Growth Factors - therapeutic use; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurodegenerative Diseases - drug therapy; Neurodegenerative Diseases - metabolism; Neurology; Organic mental disorders. Neuropsychology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Parkinson's; Nervous system diseases; Alzheimer disease; BDNF; Parkinson disease; Nerve growth factor; NGF; Trk; Cerebral disorder; Treatment; GDNF; Central nervous system disease; Glial cell line derived neurotrophic factor; Degenerative disease; Degeneration; Brain derived neurotrophic factor; Extrapyramidal syndrome; Alzheimer's
• ISSN: 0163-7258; 1879-016X; 1879-016X
• DOI: 10.1016/j.pharmthera.2013.01.004

Glial cell-derived neurotrophic factor (GDNF), and the neurotrophin 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 diseases. 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 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.