Pathomechanisms of Parkinson disease due to dysfunction of iPLA2G6
Description: PLA2G6 is known as the causative gene of familial Parkinson's disease (PARK14). Pathological studies of PARK14 revealed dopaminergic neuronal degeneration with Lewy bodies (LB). Thus, impairment of PLA2G6 may be associated with the aggregation of alpha-synuclein (AS). To reveal the association between PLA2G6 dysfunction and AS aggregation, PLA2G6 knockout Drosophila was generated and exhibited motor and sleep dysfunction due to dopaminergic neuronal degeneration. Additionally, the fly model had synaptic terminal dysfunction. These phenotypes were rescued by overexpression of wild type human PLA2G6 but not A80T pathogenic mutation. Furthermore, I found an alteration in lipid composition and AS aggregation in the brain of the fly model. Administration of linoleic acid could rescue the phenotypes and AS aggregation. Therefore, lipid composition in the brain may be critical for the mechanisms of LB formation and lipid administration therapy might have an effect on Parkinson's disease.
Amount: ¥4,680,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2016-04-01
End date: 2019-03-31
Investigator: Taku Hatano
Institution: Juntendo University
Funded outputs count: 17
Funder award ID: 16K09675
OpenAlex ID: G3511230628