Mechanism Of The LRRK2 Gene In Zebrafish Modeling Of Parkinson's Disease

Parkinson's disease is the second largest neurodegenerative disease in the world.It is characterized by the selective deletion of dopaminergic neurons in the substantia nigra pars compacta and the eosinophilic Lewy bodies in the cytoplasm.The clinical manifestations are slow movements,hands and feet.And other parts of the body tremor,body stiffness,unstable posture and other movement disorders.With the deepening of human genomics research,several pathogenic genes of Parkinson's disease have been discovered,of which LRRK2(the leucine-rich repeat kinase 2)is more special,because it is in the case of familial Parkinson's disease or in sporadic In Parkinson's disease,LRRK2(the leucine-rich repeat kinase 2)is an important pathogenic gene,making the LRRK2 gene an important target site for Parkinson's disease model.We previously used Morpolino to inhibit the expression of LRRK2 in zebrafish and established a Parkinson's disease model that showed loss of dopamine neurons and decreased activity.However,due to the temporary inhibition of Morpholino,it could not be used for large-scale drug screening.We used zinc-finger nucleases(ZFNs)to knock out LRRK2 in zebrafish,but the results showed that the mutant line showed The behavior is active.Through RNA-seq,we found that genes involved in neurological and immune diseases are significantly affected.Therefore,functional studies by antibacterial reaction experiments revealed that the antibacterial response in the LRRK2 gene mutant was attenuated.This also confirms the association of the LRRK2 gene with the immune-related disease,Crohn's disease and leprosy(Crohn's disease and leprosy).From the above results,we can conclude that immunosuppression may be a cause of Parkinson's disease,providing us with a more in-depth study of Parkinson's disease.