In human brain biopsies of patients suffering from Parkinson disease or Lewy body dementia, tubulin polymerization promoting proteins (TPPPs) have been detected in disease-related neuronal inclusions. There are 3 TPPP paralogs in human, TPPP, TPPP2, and TPPP3. There is one orthologous gene in Drosophila, Dmel\ringer, for which multiple genetic reagents have been generated including loss-of-function mutations, overexpression and RNAi targeting constructs, and alleles caused by insertional mutagenesis.
None of the three human genes, TPPP, TPPP2, or TPPP3, has been introduced into flies.
In Drosophila, animals homozygous for an amorphic ringer mutation exhibit reduced viability to adulthood. Adult survivors exhibit progressive locomotor dysfunction and reduced lifespan; progressive loss of dopaminergic neurons in the brain is observed. In wild-type, the ringer protein localizes neuronal mitochondria; mutant animals exhibit mitochondrial structural damage and dysfunctions. Administration of L-DOPA to ringer mutant animals via feeding results in amelioration of the locomotor phenotype, but not of other phenotypes.
[updated Jul. 2021 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]
Tubulin polymerization promoting proteins (TPPPs) act as regulators of microtubule dynamics by promoting microtubule nucleation and polymerization; also involved in microtubule bundling and stabilization of existing microtubules, thereby maintaining the integrity of the microtubule network. [Gene Cards, TPPP; 2021.07.10]
Many to one: 3 human genes to 1 Drosophila gene.
High-scoring ortholog of human TPPP, TPPP2, TPPP3 (1 Drosophila to 3 human). Dmel\ringer shares 38-42% identity and 51-57% similarity with the human genes.
