Authors: Georg Auburger Michael Klinkenberg Jessica Drost Katrin Marcus Blas MoralesGordo Wolfram S Kunz Ulrich Brandt Vania Broccoli Heinz Reichmann Suzana Gispert Marina Jendrach
Publish Date: 2012/02/19
Volume: 46, Issue: 1, Pages: 20-27
Abstract
Parkinsons 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 Parkinsons 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 eg the effect of stressors Furthermore since a bioenergetic deficit underlies early stage Parkinsons 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 fibroblastderived 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 Parkinsons disease Alzheimers 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 Parkinsons disease model able to serve as a complement to animal mutants transformed cell lines and patient tissues
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