Using Patient-Derived Induced Pluripotent Stem Cells to Identify Parkinson’s Disease-Relevant Phenotypes
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.
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.
KeywordsMitochondria Oxidative stress Dopaminergic neurons Alpha synuclein LRRK2 Gene editing
This work is supported by NIH grants R24OD019803 (M.E.E.), P51OD011106 (M.E.E.), NINDS T32-Neuroscience Training Program (S.C.V.), the UW-Madison Office of the Vice Chancellor for Research and Graduate Education (M.E.E.), Advancing a Healthier Wisconsin (A.D.E.), and philanthropic support to the Medical College of Wisconsin for Parkinson’s disease research (A.D.E.).
Compliance with Ethical Standards
Conflict of Interest
Allison D. Ebert, Marina Emborg, Samantha Sison and Scott Vermilyea each declare no potential conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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