Abstract book (download .pdf file) - Redox and Inflammation ...

Session 9: Neurodegenerative diseases Poster 17
Study of the role of the Parkinson’s disease gene, Park2, in the development of gliomas.
Julien Viotti, Eric Duplan, Frédéric Checler and Cristine Alves da Costa
Institut de Pharmacologie Moléculaire et Cellulaire and Institut de NeuroMédecine
Moléculaire, UMR6097 CNRS/UNSA, 660 route des Lucioles, 06560 Valbonne, France,
viotti@ipmc.cnrs.fr
Cancer is a huge age-related problem of public health that is mainly characterized by cell
death control impairment. In contrast, Parkinson’s disease (PD) is a neurodegenerative
disorder that is due to a massive loss of dopaminergic neurons of the substantia nigra by
exacerbated apoptosis. Interestingly, several epidemiological data evidenced a negative
correlation between PD and cancer. This negative correlation raises the question of whether
despite phenotypically distinct, these two diseases could share common protein effectors. In
this context, it is worth noting that most of familial PD-associated proteins are implicated in
cell cycle control and often abnormally expressed in tumors. We have just ascribed a new
function to one of them, parkin, as a transcriptional factor capable of trans-repressing p53. Of
most interest several works pinpoint the role of parkin as a potential tumor suppressor protein,
the mutations of which have been associated to glioblastoma generation. The main goal of the
present work was to explore this newly identified transcription factor function of parkin in the
etiology of human brain tumors. Our first results show that the overexpression of parkin can
increase cell viability, decrease both the number of pre-apoptotic nuclei and caspase-3 activity
and modulate cell cycle kinetics. In addition, we have observed a modulation of both parkin
protein and mRNA levels according to the grade of gliomas. Our data suggest that the
putative utilization of parkin as a brain tumor biomarker could be used in replacement of the
subjective histological analysis performed in routine to date and perhaps allow an earlier and
bona fide diagnosis of this devastating and incurable type of cerebral cancer.
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