- Tools
- Downloads
- Links
- Community
- About
- Help
FB2026_01
,
released March 12, 2026
As a key regulator of mitochondrial biogenesis, the human gene PPARGC1A (or PGC-1α) has been investigated as a therapeutic target for Parkinson disease. PPARGC1A is a member of the PGC-1 family of transcriptional coactivators for steroid receptors and nuclear receptors; they are involved in regulation of energy metabolism, mitochondrial biogenesis, and other processes. There is a single orthologous gene in Drosophila, srl, for which RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated. Dmel\srl is also orthologous to two additional members of the PGC-1 family in human, PPARGC1B and PPRC1.
None of the human PGC-1 family genes has been introduced into flies.
Animals homozygous for a severe loss-of-function mutation of Dmel\srl are viable but have a reduced adult lifespan and are small in size; females are sterile. Adults exhibit an age-dependent defect in climbing ability, loss of dopaminergic neurons in the brain, and mitochondrial defects.
Genetic overexpression of Dmel\srl rescues the disease phenotypes of two different Parkinson disease models in flies (see 'Parkinson disease 2, early-onset' FBhh0000008 and 'Parkinson disease 8' FBhh0000011). Pharmaceutical intervention using pyrroloquinoline quinone (by feeding) also ameliorates the age-dependent phenotypes of these two Parkinson disease models.
For transgenic human constructs, fly transgenic constructs and classical alleles, detailed phenotypic descriptions can be found in the allele reports; allele reports can be accessed from the gene report or by clicking on the allele symbols in the Disease Ontology and Reagent tables below.
[updated Feb. 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]
Described as PGC-1 family members (http://www.ebi.ac.uk/interpro/entry/IPR034625).
PPARGC1A (or PGC-1α), PPARGC1B (or PGC-1β)("peroxisome proliferative activated receptor, gamma, coactivator" genes) and the related PPRC1 (or PRC) encode transcriptional coactivators for steroid receptors and nuclear receptors; they are involved in regulation of energy metabolism, mitochondrial biogenesis, and other processes. [Gene Cards, PPARGC1A, PPARGC1B, PPRC1; 2018.02.27]
Many to one: 3 human to 1 Drosophila; the human genes are PPARGC1A, PPARGC1B and PPRC1.
Many to one: 3 human to 1 Drosophila; the human genes are PPARGC1A, PPARGC1B and PPRC1.
Many to one: 3 human to 1 Drosophila; the human genes are PPARGC1A, PPARGC1B and PPRC1.