Can overexpression of parkin provide a novel strategy for neuroprotection in Parkinson's disease?

Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by selective degeneration of the dopamine producing neurons in the substantia nigra. There is currently no clinically applicable therapy for treating or preventing Parkinsonian neurodegeneration. Great effort is put behind the development of novel therapeutic approaches that aim to alter the natural progression of the disease. For example, a disease-modifying Strategy based on the use of glial cell line-derived neurotrophic factor family of ligands have yielded successful results in animal models and later in initial clinical trials. More recently, identification of the gene mutations underlying the familial forms of the disease opened new frontiers in tackling the underlying neuropathological changes seen in PD brains. Overexpression of parkin, in particular, emerged as a powerful approach with complementary effects to those described with use of neurotrophic factors. In light of the fact that the mechanism of disease in the affected patient population might be significantly variable, the ability to intervene the disease process at multiple levels should be seen as a key point in devising effective treatments. (C) 2008 Elsevier Inc. All rights reserved.