Several of the human FOXO genes have been implicated in processes related to Parkinson disease. This report, 'Parkinson disease (postulated), FOXO-related', describes work done with a disease model using the Drosophila foxo gene. In Drosophila, Dmel\foxo is the single member of the O sub-group of the forkhead box family of transcription factors; there are 4 sub-group O members in human, FOXO1, FOXO3, FOXO4, and FOXO6. RNAi targeting constructs and many alleles caused by insertional mutagenesis have been generated for Dmel\foxo.
The human Hsap\FOXO3 gene has been introduced into flies, but has not been characterized in the context of this disease model.
In flies, expression of Dmel\foxo is not restricted to neural tissues, but is required for the development and survival of specific dopaminergic neurons in pupal and adult brain. Animals homozygous for an amorphic mutation of foxo exhibit progressive locomotor deficits and reduced lifespan. Extensive physical and genetic interactions have been reported for Dmel\foxo, including with several genes implicated in Parkinson disease; see below and in the foxo gene report.
[updated Oct. 2018 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]
A number of studies have implicated human FOXO genes in processes related to Parkinson disease (FBrf0238447 and references cited therein).
Of the 43 identified forkhead box transcription factors in human, there are 4 sub-group O members: FOXO1, FOXO3, FOXO4, and FOXO6 (https://www.genenames.org/cgi-bin/genefamilies/set/508).
19 genes encoding forkhead box transcription factors have been identified in Drosophila (/reports/FBgg0000750.html).
The defining feature of FOX proteins is the forkhead box, a sequence of 80 to 100 amino acids forming a motif that binds to DNA. Forkhead genes are a subgroup of the helix-turn-helix class of proteins (https://www.genenames.org/cgi-bin/genefamilies/set/508).
Many to one: 4 human to 1 Drosophila; the human genes are FOXO1, FOXO3, FOXO4, and FOXO6.
Many to one: 4 human to 1 Drosophila; the human genes are FOXO1, FOXO3, FOXO4, and FOXO6.
Many to one: 4 human to 1 Drosophila; the human genes are FOXO1, FOXO3, FOXO4, and FOXO6.
Many to one: 4 human to 1 Drosophila; the human genes are FOXO1, FOXO3, FOXO4, and FOXO6.
Moderate-scoring ortholog of human FOXO1, FOXO3, FOXO4, and FOXO6 (1 Drosophila to 4 human). Dmel\foxo shares 30-34% identity and 39-44% similarity with the human genes.
