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

Abstract

Parkinson’s disease (PD) is a complicated neurodegenerative disorder although it is of-tentimes defined by clinical motor symptoms originated from age dependent and pro-gressive 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 posttrans-lational 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 neu-rons from PD patient specific induced pluripotent stem cells (PD iPSCs), HTS techonolo-gies 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 bene-fits of PD iPSCs-derived dopaminergic neurons to screen signaling pathways that are initiated by PD linked gene mutations and thus causative for dopaminergic neurodegn-eration in PD.