Methods for Treating Parkinson’s Disease and Related Neurological Disorders

Caritas St. Elizabeth's Medical Center
posted on 02/13/2009

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Description: Parkinson disease is the second most common neurodegenerative disease affecting more than a million patients in the US. The disease is characterized by the selective loss of dopaminergic neurons in the substantia nigra, resulting in reduced dopamine contents in the stratum. Current therapeutic approaches target dopamine metabolism, but do not prevent the degeneration of dopaminergic neurons. Recently, a number of genes have been genetically linked to PD pathogenesis. The proteins encoded by these genes have been suggested to regulate oxidative stress response (a-synucein, DJ-1), protein degradation (Parkin), and mitochondrial functions (PINK-1, DJ-1, a-synuclein, Parkin). The abilities of DJ-1 to promote neuronal survival, regulate anti-oxidative stress response, and prevent protein aggregation make it an ideal therapeutic target for PD and related neurological disorders. Unlike the stable wild type DJ-1 protein, pathologic DJ-1 mutants are quickly degraded, indicating that the loss of normal DJ-1 functions contributes to disease progression. Therefore, pharmacologically increasing the DJ-1 activities in the brain may represent a novel therapeutic approach. Based on our functional studies of DJ-1, we have developed methods to identify compounds that can increase DJ-1 expression or mimic its cellular activities. Advantages: Our approach aims to increase the expression levels or to mimic the cellular functions of a proven PD-related protein that affects both dopamine synthesis and neuronal survival. Current therapeutic approaches temporarily relieve symptoms by regulating dopamine metabolism, but do not hinder neurodegeneration in the long run. By targeting a protein known to play an important role in preventing PD, we may be able to identify agents that can both control the symptoms and prevent the progression of PD. We are looking for commercial partners to further exploit this research towards the management of the DJ-1 gene expression and function for treatment of neuronal disorders, especially Parkinson disease. It should be noted that this gene may have useful applications in male fertility and breast cancer research.