title: Primary skin fibroblasts as a model of Parkinson's disease.
abstract: 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.
authors.affiliation: Experimental Neurology, Department of Neurology, Goethe University Hospital, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Auburger
authors.forename: Michael
authors.initials: M
authors.lastname: Klinkenberg
authors.forename: Jessica
authors.initials: J
authors.lastname: Drost
authors.forename: Katrin
authors.initials: K
authors.lastname: Marcus
authors.forename: Blas
authors.initials: B
authors.lastname: Morales-Gordo
authors.forename: Wolfram S
authors.initials: WS
authors.lastname: Kunz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brandt
authors.forename: Vania
authors.initials: V
authors.lastname: Broccoli
authors.forename: Heinz
authors.initials: H
authors.lastname: Reichmann
authors.forename: Suzana
authors.initials: S
authors.lastname: Gispert
authors.forename: Marina
authors.initials: M
authors.lastname: Jendrach
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008954:Models, Biological; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology* / Q000628:therapy; D012867:Skin / Q000473:pathology*; D016038:Skin Transplantation