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    Parkinson's Disease Skin Fibroblasts Display Signature Alterations in Growth, Redox Homeostasis, Mitochondrial Function, and Autophagy

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    Author
    Teves, Joji M. Y.
    Bhargava, Vedanshi
    Kirwan, Konner R.
    Corenblum, Mandi J.
    Justiniano, Rebecca
    Wondrak, Georg T.
    Anandhan, Annadurai
    Flores, Andrew J.
    Schipper, David A.
    Khalpey, Zain
    Sligh, James E.
    Curiel-Lewandrowski, Clara
    Sherman, Scott J.
    Madhavan, Lalitha
    Show allShow less
    Affiliation
    Univ Arizona, Grad Interdisciplinary Program Appl Biosci
    Univ Arizona, Undergrad Biol Res Program, Neurosci & Cognit Sci Undergrad Program
    Univ Arizona, Dept Neurol
    Univ Arizona, Pharmacol & Toxicol
    Univ Arizona, Grad Interdisciplinary Program Physiol Sci
    Univ Arizona, Dept Surg
    Univ Arizona, Dept Med
    Univ Arizona, Evelyn F McKnight Brain Inst
    Issue Date
    2018-01-12
    Keywords
    Parkinson's disease
    sporadic
    human dermal fibroblasts
    oxidative stress
    autophagy
    mitochondrial function
    UVA irradiation
    
    Metadata
    Show full item record
    Publisher
    FRONTIERS MEDIA SA
    Citation
    Parkinson's Disease Skin Fibroblasts Display Signature Alterations in Growth, Redox Homeostasis, Mitochondrial Function, and Autophagy 2018, 11 Frontiers in Neuroscience
    Journal
    Frontiers in Neuroscience
    Rights
    © 2018 Teves, Bhargava, Kirwan, Corenblum, Justiniano, Wondrak, Anandhan, Flores, Schipper, Khalpey, Sligh, Curiel-Lewandrowski, Sherman and Madhavan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
    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
    The discovery of biomarkers for Parkinson's disease (PD) is challenging due to the heterogeneous nature of this disorder, and a poor correlation between the underlying pathology and the clinically expressed phenotype. An ideal biomarker would inform on PD-relevant pathological changes via an easily assayed biological characteristic, which reliably tracks clinical symptoms. Human dermal (skin) fibroblasts are accessible peripheral cells that constitute a patient-specific system, which potentially recapitulates the PD chronological and epigenetic aging history. Here, we compared primary skin fibroblasts obtained from individuals diagnosed with late-onset sporadic PD, and healthy age-matched controls. These fibroblasts were studied from fundamental viewpoints of growth and morphology, as well as redox, mitochondrial, and autophagic function. It was observed that fibroblasts from PD subjects had higher growth rates, and appeared distinctly different in terms of morphology and spatial organization in culture, compared to control cells. It was also found that the PD fibroblasts exhibited significantly compromised mitochondrial structure and function when assessed via morphological and oxidative phosphorylation assays. Additionally, a striking increase in baseline macroautophagy levels was seen in cells from PD subjects. Exposure of the skin fibroblasts to physiologically relevant stress, specifically ultraviolet irradiation (UVA), further exaggerated the autophagic dysfunction in the PD cells. Moreover, the PD fibroblasts accumulated higher levels of reactive oxygen species (ROS) coupled with lower cell viability upon UVA treatment. In essence, these studies highlight primary skin fibroblasts as a patient-relevant model that captures fundamental PD molecular mechanisms, and supports their potential utility to develop diagnostic and prognostic biomarkers for the disease.
    ISSN
    1662-453X
    DOI
    10.3389/fnins.2017.00737
    Version
    Final published version
    Sponsors
    University of Arizona; Arizona Center for the Biology of Complex Diseases grant; Cancer Center confocal core [P30 CA023074]; USAID-Science Technology Research Innovation for Development (STRIDE) scholarship
    Additional Links
    http://journal.frontiersin.org/article/10.3389/fnins.2017.00737/full
    ae974a485f413a2113503eed53cd6c53
    10.3389/fnins.2017.00737
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