Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism

  title={Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism},
  author={Vincenzo Bonifati and Patrizia Rizzu and Marijke J. van Baren and Onno Schaap and Guido J. Breedveld and Elmar Krieger and Marieke C Dekker and Ferdinando Squitieri and Pablo Ib{\'a}{\~n}ez and Marijke Joosse and Jeroen W. van Dongen and Nicola Vanacore and John Cornelis van Swieten and Alexis Brice and Giuseppe Meco and Cornelia M. van Duijn and Ben A. Oostra and Peter Heutink},
  pages={256 - 259}
The DJ-1 gene encodes a ubiquitous, highly conserved protein. Here, we show that DJ-1 mutations are associated with PARK7, a monogenic form of human parkinsonism. The function of the DJ-1 protein remains unknown, but evidence suggests its involvement in the oxidative stress response. Our findings indicate that loss of DJ-1 function leads to neurodegeneration. Elucidating the physiological role of DJ-1 protein may promote understanding of the mechanisms of brain neuronal maintenance and… 

Screening for DJ-1 mutations in early onset autosomal recessive parkinsonism

No mutations were found in the screening series for DJ-1 mutations, indicating that PARK7 is not a common locus for early onset autosomal recessive parkinsonism, and that one or more new loci remains to be identified.

Expression of DJ-1 in Neurodegenerative Disorders.

This chapter provides an overview on the expression of DJ-1 mRNA and protein in different neurodegenerative disorders and discusses some of its main functions together withDJ-1's potential for neuroprotection.

DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism

Evidence from genetic studies on the yeast DJ-1 homologue, and biochemical studies in murine and human cell lines, suggests a role forDJ-1 as an antioxidant and/or a molecular chaperone, and this will lead to a better understanding of the pathogenesis of DJ- 1-related and common forms of Parkinson’s disease.

DJ-1 mutations in Parkinson's disease.

It was confirmed that PARK6 and PARK7 (DJ-1), despite being phenotypically similar and mapping to the same small chromosomal region of 1p36, are caused by mutations in separate genes.

Assessment of a DJ-1 (PARK7) polymorphism in Finnish PD

The authors analyzed whether a polymorphism within exon 1 of DJ-1 contributes to the risk of sporadic PD in a Finnish case-control series and found that this gene does not play a major role in the genetic predisposition to PD in this population.

PET neuroimaging and mutations in the DJ-1 gene

Mutations in the DJ-1 gene lead to autosomal recessive early-onset parkinsonism, with reduced F-DOPA uptake concordant with typical Parkinson’s disease and in the, clinically unaffected, heterozygous relatives, F- DOPA metabolism was unremarkable, thus not suggesting a dosage effect of the DJThe1 gene.

The biochemistry of Parkinson's disease.

  • M. Cookson
  • Biology
    Annual review of biochemistry
  • 2005
Several genes have been identified for monogenic disorders that variably resemble Parkinson's disease, but it is not yet fully resolved how the recessive genes relate to alpha-synuclein, or whether they represent different ways to induce a similar phenotype.

DJ-1 Mutations are Rare in a Swedish Parkinson Cohort

The hypothesis that alterations in DJ-1 are not a common cause of familial and early-onset PD world-wide is strengthened, as a possible small effect of Ala167Ala onDJ-1 gene function is shown.

The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease.

It is concluded that DJ-1 is not an essential component of LBs and Lewy neurites, is expressed mainly by astrocytes in human brain tissue and is sensitive to oxidative stress conditions, consistent with the hypothesis that neuronal-glial interactions are important in the pathophysiology of Parkinson's disease.



Recent advances in the genetics and pathogenesis of Parkinson disease

Analysis of the structure and function of these gene products point to the critical role of protein aggregation in dopaminergic neurons of the substantia nigra as the common mechanism leading to neurodegeneration in all known forms of this disease.

Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36.

A large Sicilian family with four definitely affected members (the Marsala kindred) was identified, characterized by early-onset parkinsonism, with slow progression and sustained response to levodopa, and the Parkin-associated phenotype is broad, and some cases are indistinguishable from idiopathic PD.

Localization of autosomal recessive early‐onset parkinsonism to chromosome 1p36 (PARK7) in an independent dataset

Location of autosomal recessive early‐onset parkinsonism to PARK7 is confirmed, suggesting it to be a frequent locus, and assignment of families to either PARK6 or PARK7 might be difficult because of the proximity of the two loci on chromosome 1p.

Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36.

It is concluded that on chromosome 1 a second locus, PARK7, involved in autosomal recessive, early-onset parkinsonism is identified.

Effect of Wild-type or Mutant Parkin on Oxidative Damage, Nitric Oxide, Antioxidant Defenses, and the Proteasome*

The presence of mutant Parkin in substantia nigra in juvenile parkinsonism may increase oxidative stress and nitric oxide production, sensitizing cells to death induced by other insults, and be blocked by the proteasome inhibitor, lactacystin.

DJ-1 Positively Regulates the Androgen Receptor by Impairing the Binding of PIASxα to the Receptor*

Results indicate that DJ-1 is a positive regulator of the androgen receptor, which is a novel candidate of the oncogene product that transformed mouse NIH3T3 cells in cooperation with an activated ras.

DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras.

DJ-1 showed a cooperative transforming activity with H-Ras, more than 3 times as strong as the activity of ras/myc combination and is suggested to be a novel mitogen-dependent oncogene product involved in a Ras-related signal transduction pathway.

α-Synuclein Protects against Oxidative Stress via Inactivation of the c-Jun N-terminal Kinase Stress-signaling Pathway in Neuronal Cells*

Results suggest that increased α-synuclein expression might protect cells from oxidative stress by inactivation of JNK via increased expression of JIP-1b/IB1, which may play a mutual role in the neuronal response to injury and neurodegeneration.

Identification and characterization of a novel protein that regulates RNA–protein interaction

It is reported that the RBP is a complex protein of about 400 kDa, composed of RNA‐binding subunit (RBS), and regulatory subunit(s) (RS), and the cDNA contains the complete coding sequence because the recombinant protein has the same electrophoretic mobility as that of the native RS in SDS‐polyacrylamide gels.