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http://dx.doi.org/10.4051/ibc.2012.4.3.0006

Systemic and Cell-Type Specific Profiling of Molecular Changes in Parkinson's Disease  

Lee, Yunjong (Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Departments of Physiology, and Neurology, the Johns Hopkins University School of Medicine)
Publication Information
Interdisciplinary Bio Central / v.4, no.3, 2012 , pp. 6.1-6.12 More about this Journal
Abstract
Parkinson's disease (PD) is a complicated neurodegenerative disorder although it is oftentimes defined by clinical motor symptoms originated from age dependent and progressive loss of dopaminergic neurons in the midbrain. The pathogenesis of PD involves dopaminergic and nondopaminergic neurons in many brain regions and the molecular mechanisms underlying the death of different cell types still remain to be elucidated. There are indications that PD causing disease processes occur in a global scale ranging from DNA to RNA, and proteins. Several PD-associated genes have been reported to play diverse roles in controlling cellular functions in different levels, such as chromatin structure, transcription, processing of mRNA, translational modulation, and posttranslational modification of proteins. The advent of quantitative high throughput screening (HTS) tools makes it possible to monitor systemic changes in DNA, RNA and proteins in PD models. Combined with dopamine neuron isolation or derivation of dopamine neurons from PD patient specific induced pluripotent stem cells (PD iPSCs), HTS techonologies will provide opportunities to draw PD causing sequences of molecular events in pathologically relevant PD samples. Here I discuss previous studies that identified molecular functions in which PD genes are involved, especially those signaling pathways that can be efficiently studied using HTS methodologies. Brief descriptions of quantitative and systemic tools looking at DNA, RNA and proteins will be followed. Finally, I will emphasize the use and potential benefits of PD iPSCs-derived dopaminergic neurons to screen signaling pathways that are initiated by PD linked gene mutations and thus causative for dopaminergic neurodegneration in PD.
Keywords
Parkinson's disease; cell type specific; high-throughput; systemic; quantitative profiles; dopaminergic neuron; neurodegeneration; induced pluripotent stem cell;
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