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FB2026_01
,
released March 12, 2026
This report describes Parkinson disease 7 (PARK7, PD7), which is a subtype of Parkinson disease; PARK7 exhibits autosomal recessive inheritance. The human gene implicated in this disease is PARK7 (DJ-1), which contains a single highly conserved domain and functions as a dimer; it plays a role in protection against oxidative stress. There are two fly orthologs, dj-1β and DJ-1α, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. The two Drosophila orthologs show very different expression patterns: dj-1β is expressed at moderate to high levels throughout development and in most tissues assayed; DJ-1α is expressed primarily, but not exclusively, in testis.
Defective responses to oxidative stress plays a role in a number of neurodegenerative diseases (Chen et al., 2012, PMID_25774178); the set of dopaminergic neurons affected in Parkinson disease are among those that are particularly sensitive to damage caused by oxidative stress (Wang and Michaelis, 2010, FBrf0228585). The human PARK7 (DJ-1) gene acts as a stress sensor and subsequently acts in several diverse capacities to ameliorate negative consequences of high levels of oxidative stress (FBrf0228447).
Several independent UAS constructs of the wild-type human gene, Hsap\PARK7, have been introduced into flies. Heterologous rescue (functional complementation) of some aspects of the phenotypes of a null Dmel\dj-1β mutation and of a Dmel\DJ-1α insertion mutation have been demonstrated.
Loss-of-function mutations in the Dmel\dj-1β gene are viable and fertile; observed phenotypes include aspects relevant to Parkinson disease, such as locomotor behavior defective and oxidative stress response defective. Physical interactions of the Dmel\dj-1β protein product have been described; see below and in the dj-1β gene report. Loss-of-function mutations in the Dmel\DJ-1α gene produce conflicting results: some are lethal, others are viable and fertile; RNAi-generated phenotypes include chemical resistant, locomotor behavior defective, and stress response defective. Phenotypic assays using the fly genes have allowed characterization of genetic interactions.
Therapeutic drug candidates have been administered by feeding and tested using several different phenotypic assays.
[updated Dec. 2016 by FlyBase; FBrf0222196]
Parkinson disease (PD) is a neurodegenerative disease usually typified by slow onset in mid to late adulthood; there are also early-onset and juvenile forms of the disease. Symptoms worsen over time and include resting tremor, muscular rigidity, bradykinesia [abnormal slowness of movement], and postural instability [impaired balance and coordination]; additional symptoms may include postural abnormalities, dysautonomia [symptoms caused by malfunction of the autonomic nervous system], dystonic cramps, and dementia. Parkinson disease is the second-most common neurodegenerative disease (after Alzheimer disease), affecting approximately 1% of the population over 50 (Polymeropoulos et al., 1996, pubmed:8895469). [from MIM:168600; 2013.07.23]
Parkinson disease is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 may be referred to as juvenile-onset disease. [from Genetics Home Reference, GHR_condition:parkinson-disease, 2015.02.13]
[PARKINSON DISEASE 7, AUTOSOMAL RECESSIVE EARLY-ONSET; PARK7](https://omim.org/entry/606324)
[ONCOGENE DJ1; DJ1](https://omim.org/entry/602533)
Parkinson disease 7 is characterized by typical symptoms of Parkinson disease (described above); psychiatric symptoms may be observed. Early onset is typically observed; disease progression is usually slow. (Van Duijn et al., 2001, pubmed:11462174) [from MIM:606324; 2015.02.16]
Parkinson disease 7 exhibits an autosomal recessive pattern of transmission; shown to be caused by mutation(s) in the PARK7 (DJ1) gene. [from MIM:606324; 2015.02.16]
DJ-1 has an atypical peroxiredoxin-like peroxidase activity that is involved in scavenging mitochondrial hydrogen peroxide (Andres-Mateos et al., 2007, PMID_17766438). Translocation of DJ-1 into mitochondria is enhanced by oxidative stress and is mediated by C106 oxidation (Canet-Aviles et al., 2004, PMID_15181200).
Dj-1 is a multi-functional protein that mediates an antioxidative stress reaction at several levels, including enzymatically, via transcriptional regulation, and as a chaperone. Its activity is regulated by oxidative status, especially that of cysteine 106 (C106).
PARK7 (DJ1) protein has multiple functions including a chaperone with protease activity (response to cellular oxidative stress), a transcriptional regulator, and an antioxidant scavenger and redox sensor. PARK7 protein is also involved in tumorigenesis and in maintaining mitochondrial homeostasis (summary by Ottolini et al., 2013, pubmed:23418303). [from MIM:602533; 2015.02.16]
One to many: 1 human to 2 Drosophila.
Ortholog of human PARK7 (2 Drosphila to 1 human). Dmel\dj-1β shares 53% identity and 70% similarity with human PARK7.
Ortholog of human PARK7 (2 Drosphila to 1 human). Dmel\DJ-1α shares 56% identity and 70% similarity with human PARK7.