Journal Article

The DJ-1<sup>L166P</sup> mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes

Maria G. Macedo, Burcu Anar, Iraad F. Bronner, Milena Cannella, Ferdinando Squitieri, Vincenzo Bonifati, André Hoogeveen, Peter Heutink and Patrizia Rizzu

in Human Molecular Genetics

Volume 12, issue 21, pages 2807-2816
Published in print November 2003 | ISSN: 0964-6906
Published online November 2003 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddg304
The DJ-1L166P mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes

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Parkinson's disease (PD) is a common neurodegenerative disorder that involves the selective degeneration of midbrain dopaminergic neurons. Recently DJ-1 mutations have been linked to autosomal-recessive early-onset Parkinsonism in two European families. By using gel filtration assays under physiological conditions we demonstrate that DJ-1 protein forms a dimeric structure. Conversely, the DJ-1L166P mutant protein shows a different elution profile as compared with DJ-1WT both in overexpression cellular systems or in lymphoblasts cells, suggesting that it might form higher order protein structures. Furthermore we observed that the level of DJ-1L166P mutant protein in the patient's lymphoblasts was very low as compared with the wild-type protein. We excluded a potential transcriptional impairment by performing quantitative RT–PCR on the patient's material. Pulse-chase experiments in transfected COS-1 cells and cycloheximide treatment in control and patient lymphoblasts indicated that the mutant protein was rapidly degraded. This rapid turnover and the structural changes of DJ-1L166P mutant protein might be crucial in the disease pathogenesis.

Journal Article.  6404 words.  Illustrated.

Subjects: Genetics and Genomics

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