S L Sison1, S C Vermilyea2,3, M E Emborg2,3,4, A D Ebert5,6. 1. Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, BSB 409, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA. 2. Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, 53705, USA. 3. Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA. 4. Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, 53705, USA. 5. Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, BSB 409, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA. aebert@mcw.edu. 6. Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. aebert@mcw.edu.
Abstract
PURPOSE OF REVIEW: Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting older individuals. The specific cause underlying dopaminergic (DA) neuron loss in the substantia nigra, a pathological hallmark of PD, remains elusive. Here, we highlight peer-reviewed reports using induced pluripotent stem cells (iPSCs) to model PD in vitro and discuss the potential disease-relevant phenotypes that may lead to a better understanding of PD etiology. Benefits of iPSCs are that they retain the genetic background of the donor individual and can be differentiated into specialized neurons to facilitate disease modeling. RECENT FINDINGS: Mitochondrial dysfunction, oxidative stress, ER stress, and alpha-synuclein accumulation are common phenotypes observed in PD iPSC-derived neurons. New culturing technologies, such as directed reprogramming and midbrain organoids, offer innovative ways of investigating intraneuronal mechanisms of PD pathology. PD patient-derived iPSCs are an evolving resource to understand PD pathology and identify therapeutic targets.
PURPOSE OF REVIEW: Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting older individuals. The specific cause underlying dopaminergic (DA) neuron loss in the substantia nigra, a pathological hallmark of PD, remains elusive. Here, we highlight peer-reviewed reports using induced pluripotent stem cells (iPSCs) to model PD in vitro and discuss the potential disease-relevant phenotypes that may lead to a better understanding of PD etiology. Benefits of iPSCs are that they retain the genetic background of the donor individual and can be differentiated into specialized neurons to facilitate disease modeling. RECENT FINDINGS:Mitochondrial dysfunction, oxidative stress, ER stress, and alpha-synuclein accumulation are common phenotypes observed in PD iPSC-derived neurons. New culturing technologies, such as directed reprogramming and midbrain organoids, offer innovative ways of investigating intraneuronal mechanisms of PD pathology. PDpatient-derived iPSCs are an evolving resource to understand PD pathology and identify therapeutic targets.
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