Parallel neurodegenerative phenotypes in sporadic Parkinson's disease fibroblasts and midbrain dopamine neurons
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Author
Corenblum, M.J.McRobbie-Johnson, A.
Carruth, E.
Bernard, K.
Luo, M.
Mandarino, L.J.
Peterson, S.
Sans-Fuentes, M.A.
Billheimer, D.
Maley, T.
Eggers, E.D.
Madhavan, L.
Affiliation
Department of Neurology, University of ArizonaPhysiological Sciences Graduate Program, University of Arizona
Department of Medicine, University of Arizona
Statistical Consulting Lab, BIO5 Institute, University of Arizona
Departments of Physiology and Biomedical Engineering, University of Arizona
Evelyn F McKnight Brain Institute and BIO5 Institute, University of Arizona
Issue Date
2023-10Keywords
AgingHuman Induced Pluripotent Stem Cells
Midbrain Dopamine Neurons
Mitochondrial Dysfunction
Parkinson's disease
Skin fibroblasts
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Elsevier LtdCitation
Corenblum, M. J., et al. "Parallel neurodegenerative phenotypes in sporadic Parkinson’s disease fibroblasts and midbrain dopamine neurons." Progress in Neurobiology 229 (2023): 102501.Journal
Progress in NeurobiologyRights
© 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Understanding the mechanisms causing Parkinson's disease (PD) is vital to the development of much needed early diagnostics and therapeutics for this debilitating condition. Here, we report cellular and molecular alterations in skin fibroblasts of late-onset sporadic PD subjects, that were recapitulated in matched induced pluripotent stem cell (iPSC)-derived midbrain dopamine (DA) neurons, reprogrammed from the same fibroblasts. Specific changes in growth, morphology, reactive oxygen species levels, mitochondrial function, and autophagy, were seen in both the PD fibroblasts and DA neurons, as compared to their respective controls. Additionally, significant alterations in alpha synuclein expression and electrical activity were also noted in the PD DA neurons. Interestingly, although the fibroblast and neuronal phenotypes were similar to each other, they differed in their nature and scale. Furthermore, statistical analysis revealed potential novel associations between various clinical measures of the PD subjects and the different fibroblast and neuronal data. In essence, these findings encapsulate spontaneous, in-tandem, disease-related phenotypes in both sporadic PD fibroblasts and iPSC-based DA neurons, from the same patient, and generates an innovative model to investigate PD mechanisms with a view towards rational disease stratification and precision treatments. © 2023 The AuthorsNote
Open access articleISSN
0301-0082PubMed ID
37451330Version
Final Published Versionae974a485f413a2113503eed53cd6c53
10.1016/j.pneurobio.2023.102501
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Except where otherwise noted, this item's license is described as © 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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