Concise Review: Therapeutic Strategies for Parkinson Disease Based on the Modulation of Adult Neurogenesis

Abstract

Abstract Parkinson disease (PD) is a progressive neurodegenerative disorder affecting millions of people worldwide. To date, treatment strategies are mainly symptomatic and aimed at increasing dopamine levels in the degenerating nigrostriatal system. Hope rests upon the development of effective neurorestorative or neuroregenerative therapies based on gene and stem cell therapy or a combination of both. The results of experimental therapies based on transplanting exogenous dopamine-rich fetal cells or glial cell line-derived neurotrophic factor overexpression into the brain of Parkinson disease patients encourage future cell- and gene-based strategies. The endogenous neural stem cells of the adult brain provide an alternative and attractive cell source for neuroregeneration. Prior to designing endogenous stem cell therapies, the possible impact of PD on adult neuronal stem cell pools and their neurogenic potential must be investigated. We review the experimental data obtained in animal models or based on analysis of patients' brains prior to describing different treatment strategies. Strategies aimed at enhancing neuronal stem cell proliferation and/or differentiation in the striatum or the substantia nigra will have to be compared in animal models and selected prior to clinical studies.