The human gene SREBF1 (sterol regulatory element binding transcription factor 1) has been identified in a genome-wide association study (GWAS) as a possible susceptibility locus for Parkinson disease. SREBP1, and the related gene SREBP2, are (bHLH-Zip) transcription factors that control cholesterol and lipid homeostasis by stimulating transcription of sterol-regulated genes. There is a single orthologous gene in Drosophila, SREBP, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Neither of the human genes, SREBF1 nor SREBP2, has been introduced into flies.
SREBP was identified in a genome-wide RNAi screen in Drosophila S2R+ cells to identify genes that promote or inhibit park translocation and mitophagy following mitochondrial depolarization (FBrf0226429). Provision of exogenous lipids ameliorates the effect, thus suggesting a role for lipid metabolism in the regulation of mitophagy following loss of membrane potential.
Homozygous loss-of-function mutations of Dmel\SREBP are lethal, usually during the larval stages. Systemic loss of function effected by RNAi results in a dose-dependent developmental delay and lethality during larval and pupal stages. Surviving adults show a significant reduction in body size, body weight and wing area. Genetic interactions of SREBP have been described; see the SREBP gene report.
[updated May 2017 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 OMIM:168600; 2013.07.23]
A GWAS analysis has associated a variant of the SREBF1 locus with onset of sporadic Parkinson disease (see GWAS Catalog, below in 'External links').
Sterol regulatory element-binding protein-1 (SREBP1) and SREBP2 are structurally related proteins that control cholesterol homeostasis by stimulating transcription of sterol-regulated genes (summary by Osborne, 2001; pubmed:1485982). [from OMIM:184756; 2017.05.02]
SREBF1 encodes a transcription factor that binds to the sterol regulatory element-1 (SRE1); the protein is a member of the basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor family. [Gene Cards, SREBF1; 2017.05.02]
Many to one: 2 human to 1 Drosophila; second human gene is SREBF2.