Neuregulins, Neuroprotection and Parkinson's Disease
Annual rept. 19 Nov 2001-18 Nov 2002
KENTUCKY UNIV LEXINGTON
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Although the basic underlying mechanisms of Parkinsons disease remain unknown, considerable efforts have centered on developing effective strategies for halting the neurodegenerative process and restoring normal function. One promising approach involves the potential therapeutic use of neurotrophic factors. The main hypothesis being tested in this research project is that the neuregulin glial growth factor-2 GGF2, a neural growthdifferentiation factor, is neuroprotective andor neurorestorative for the damaged dopaminergic nigrostriatal system. Our present results provide good evidence that GGF2 can function as a neurotrophic factor for nigrostriatal dopaminergic neurons. Studies in vivo demonstrate that administration of GGF2 to the normal nigrostriatal system enhances striatal dopamine release. This is important because compounds that can stimulate the secretion or release of dopamine in the nigrostriatal system have the potential for overcoming the lack of dopamine neuronal function in Parkinsons disease patients. Results from in vitro experiments show that GGF2 protects cultured midbrain neurons against injury, most notably neurotoxin-induced degeneration. In addition, treatment of the cultures with GGF2 promotes the long-term survival of the developing dopamine cells. Thus, GGF2 exhibits trophic actions for mesencephalic dopamine neurons, which may be mediated in part via glial mechanisms. Overall, results from these studies may form the basis for the therapeutic application of neuregulins to the treatment of neurotoxin-induced neurodegenerative disorders such as Parkinsons disease.
- Medicine and Medical Research