Growth Factors in Parkinson’s Disease
There is currently intense interest in the possible role of neurotrophic factors in neurodegenerative diseases, because deficiencies may play an etiological role and administration may have therapeutic effects (Hefti et al., 1989, 1990). Particular attention has been focused on Alzheimer’s disease (AD) and Parkinson’s disease (PD), the former because of the importance of nerve growth factor (NGF) in maintaining basal forebrain cholinergic neurons. With regard to PD, the possibility that transplants may be helpful because of the stimulation of neurotrophic activity has been mooted, and NGF has even been tried clinically as a method of promoting the survival of adrenal medulla cells grafted into the basal ganglia (Olson et al, 1991; Silani et al., 1990). In more basic work, a number of identified factors have been shown to promote survival of dopamine neurons in culture or to protect such cultured neurons against neurotoxins such as 6-hydroxydopamine (6-OHDA) or MPP+, the active principle of MPTP.
KeywordsNerve Growth Factor Substantia Nigra Dopaminergic Neuron Basic Fibroblast Growth Factor Basal Forebrain Cholinergic Neuron
Unable to display preview. Download preview PDF.
- Knüsel B, Michel PP, Schwaber JS, Hefti F (1990): Selective and nonselective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors I and II. J Neurosci10:558–570PubMedGoogle Scholar
- Knüsel B, Beck KD, Winslow JW, Rosenthal A, Burton LE, Widmer HR, Nikolics K, Hefti F (1992): Brain-derived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain. J Neurosci12:4391–4402PubMedGoogle Scholar
- Lapchak PA, Beck KD, Araujo DM, Irwin I, Langston JW, Hefti F (1993): Chronic intranigral administration of brain-derived neurotrophic factor produces striatal dopaminergic hypofunction in unlesioned adult rats and fails to attenuate the decline of striatal dopaminergic function following medial forebrain bundle transection. Neuroscience53:639–650PubMedCrossRefGoogle Scholar
- Olson L, Backlund E-O, Ebendal T, Freedman R, Hamberger B, Hansson P, Hoffer B, Lindblom U, Meyerson B, Strömberg I, Sydow O, Sciger Å (1991): Intraputaminal infusion of nerve growth factor to support adrenal medullary autografts in Parkinson’s disease. One-year follow-up of first clinical trial. Arch Neurol48:373–381PubMedCrossRefGoogle Scholar
- Zarow C, Chui HC (1991): A simple method for assessing neuronal number in the human substantia nigra. Soc Neurosci Abstr17:1450.Google Scholar