TY  - JOUR
A1  - Auburger, Georg
A1  - Klinkenberg, Michael
A1  - Drost, Jessica
A1  - Marcus, Katrin
A1  - Morales-Gordo, Blas
A1  - Kunz, Wolfram S.
A1  - Brandt, Ulrich
A1  - Broccoli, Vania
A1  - Reichmann, Heinz
A1  - Gispert, Suzana
A1  - Jendrach, Marina
T1  - Primary skin fibroblasts as a model of Parkinson's disease
T2  - Molecular neurobiology
N2  - Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues.
KW  - Skin fibroblast
KW  - Parkinson's disease
KW  - PARK6
KW  - PARK2
KW  - PARK7
KW  - iPS
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27964
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-279643
SN  - 1559-1182
SN  - 0893-7648
N1  - Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
VL  - 46
SP  - 20
EP  - 27
PB  - Humana Press
CY  - Totowa, NJ
ER  -