Prospects for the treatment of Parkinson's disease using neurotrophic factors.
Parkinson's disease (PD) is a debilitating neurodegenerative condition that is characterised by a progressive loss of dopaminergic neurones of the substantia nigra pars compacta (SNpc) and the presence of alpha-synuclein cytoplasmic inclusions (Lewy bodies). Cardinal symptoms include tremor, bradykinesia, and rigidity, although cognitive and autonomic disturbances are not uncommon. Pharmacological treatment targeting the dopaminergic network is relatively effective at ameliorating these symptoms, especially in the early stages of the disease, but none of these therapies are curative and they generate their own problems. As dopaminergic neuronal death in PD occurs in a gradual manner, it is amenable to treatments that can either protect remaining dopaminergic neurones or prevent death of those neurones that have begun to die. Use of neurotrophic factors is a potential candidate, as various factors have been shown to increase dopaminergic neuronal survival in culture and promote survival and axonal growth in animal models of PD. Glial cell line-derived neurotrophic factor (GDNF) is currently the most effective substance that has been intensively studied and shown to have a specific 'dopaminotrophic' effect. This review will therefore focus on studies that have investigated GDNF and discuss the potential for neurotrophic factor treatment in PD.
Hurelbrink
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Cambridge Centre for Brain Repair, Addenbrooke's Hospital, Cambridge CB2 2PY, UK. cbh20@cam.ac.uk
Barker
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D000818:Animals; D016380:Brain Tissue Transplantation; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000601:surgery; D013378:Substantia Nigra / Q000637:transplantation
C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins