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dc.contributor.authorTeves, Joji M. Y.
dc.contributor.authorBhargava, Vedanshi
dc.contributor.authorKirwan, Konner R.
dc.contributor.authorCorenblum, Mandi J.
dc.contributor.authorJustiniano, Rebecca
dc.contributor.authorWondrak, Georg T.
dc.contributor.authorAnandhan, Annadurai
dc.contributor.authorFlores, Andrew J.
dc.contributor.authorSchipper, David A.
dc.contributor.authorKhalpey, Zain
dc.contributor.authorSligh, James E.
dc.contributor.authorCuriel-Lewandrowski, Clara
dc.contributor.authorSherman, Scott J.
dc.contributor.authorMadhavan, Lalitha
dc.date.accessioned2018-02-12T16:35:22Z
dc.date.available2018-02-12T16:35:22Z
dc.date.issued2018-01-12
dc.identifier.citationParkinson's Disease Skin Fibroblasts Display Signature Alterations in Growth, Redox Homeostasis, Mitochondrial Function, and Autophagy 2018, 11 Frontiers in Neuroscienceen
dc.identifier.issn1662-453X
dc.identifier.doi10.3389/fnins.2017.00737
dc.identifier.urihttp://hdl.handle.net/10150/626553
dc.description.abstractThe 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.
dc.description.sponsorshipUniversity 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) scholarshipen
dc.language.isoenen
dc.publisherFRONTIERS MEDIA SAen
dc.relation.urlhttp://journal.frontiersin.org/article/10.3389/fnins.2017.00737/fullen
dc.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).en
dc.subjectParkinson's diseaseen
dc.subjectsporadicen
dc.subjecthuman dermal fibroblastsen
dc.subjectoxidative stressen
dc.subjectautophagyen
dc.subjectmitochondrial functionen
dc.subjectUVA irradiationen
dc.titleParkinson's Disease Skin Fibroblasts Display Signature Alterations in Growth, Redox Homeostasis, Mitochondrial Function, and Autophagyen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Grad Interdisciplinary Program Appl Bioscien
dc.contributor.departmentUniv Arizona, Undergrad Biol Res Program, Neurosci & Cognit Sci Undergrad Programen
dc.contributor.departmentUniv Arizona, Dept Neurolen
dc.contributor.departmentUniv Arizona, Pharmacol & Toxicolen
dc.contributor.departmentUniv Arizona, Grad Interdisciplinary Program Physiol Scien
dc.contributor.departmentUniv Arizona, Dept Surgen
dc.contributor.departmentUniv Arizona, Dept Meden
dc.contributor.departmentUniv Arizona, Evelyn F McKnight Brain Insten
dc.identifier.journalFrontiers in Neuroscienceen
dc.description.collectioninformationThis 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.en
dc.eprint.versionFinal published versionen
refterms.dateFOA2018-06-29T10:30:14Z
html.description.abstractThe 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.


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