Stemming the Hype: What Can We Learn from IPSC Models of Parkinson's Disease and How Can We Learn It?
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Parkinson's disease (PD) is a prevalent and debilitating neurodegenerative disorder for which there are no available cures. PD pathogenesis is poorly understood because appropriate animal and in vitro models are lacking. The development of induced Pluripotent Stem Cells (iPSCs) has allowed researchers to generate disease-specific dopaminergic neurons in vitro by reprogramming skin cells from patients with the disease. It is hoped that this unprecedented access to PD patients' neurons will yield mechanistic insights into PD pathogenesis, a platform for drug screening, and a means of early diagnosis. In this article I critically evaluate the current usage of iPSCs in PD research. I first outline the iPSC paradigm and emphasise the benefits of this approach for modelling PD. I then ask what we can learn from the iPSC-based studies done to date. I argue that these studies have not been particularly informative when considered as an isolated body of evidence. I suggest that the limitations of this technology can be overcome, and I conclude that iPSCs have the potential to be an extremely useful tool in PD research. However, they will never be a panacea and should continue to be used in concert with other in vitro and animal models.
Induced pluripotent stem cells: a tool for modeling Parkinson's disease.
Bose A, Petsko G, Studer L Trends Neurosci. 2022; 45(8):608-620.
PMID: 35667922 PMC: 9576003. DOI: 10.1016/j.tins.2022.05.001.
A compendious summary of Parkinson's disease patient-derived iPSCs in the first decade.
Ren C, Wang F, Guan L, Cheng X, Zhang C, Geng D Ann Transl Med. 2020; 7(22):685.
PMID: 31930086 PMC: 6944564. DOI: 10.21037/atm.2019.11.16.
Gonzalez-Casacuberta I, Juarez-Flores D, Moren C, Garrabou G Front Neurosci. 2019; 13:894.
PMID: 31551675 PMC: 6748355. DOI: 10.3389/fnins.2019.00894.
Katt M, Mayo L, Ellis S, Mahairaki V, Rothstein J, Cheng L Fluids Barriers CNS. 2019; 16(1):20.
PMID: 31303172 PMC: 6628493. DOI: 10.1186/s12987-019-0139-4.
The Skin and Parkinson's Disease: Review of Clinical, Diagnostic, and Therapeutic Issues.
Skorvanek M, Bhatia K Mov Disord Clin Pract. 2018; 4(1):21-31.
PMID: 30363435 PMC: 6174479. DOI: 10.1002/mdc3.12425.