Preliminary Functional Study Of RAB39B Gene In Parkinson's Disease

Parkinson's disease(PD)is one of the most common neurodegenerative diseases in middle-aged and elderly people,and its incidence is second only to that of Alzheimer's disease(Alzheimer's disease,AD).The main clinical manifestation of PD is myotonic(hypokinetic rigidity),Static tremor(tremor),delayed(bradykinesia)and postural gait instability(postural instability),etc.The cellular and molecular pathogenesis of PD is not well understood.However,a large number of studies have shown that abnormal clearance of ?-synuclein protein and dysfunction of mitochondria may be the main factors of neuronal degeneration in PD.An important pathological feature of PD is that it can be found in the brain of patients after death.There are connotations formed by a-synuclein protein aggregation in neuronal cells Mutations in the gene(SNCA),which encodes ?-synuclein,lead to PD.In addition,mutations in the encoding genes of PINK1 and PARKIN proteins,which play an important role in maintaining mitochondrial homeostasis and participating in mitochondrial autophagy,have also been found to be closely related to PD.In recent years,new genes have been found to be associated with the pathogenesis of PD,including the RAB39B gene to be studied in this project.In this paper,we constructed Rab39b deficient mice by TALEN technique.Both male and female mice survived and were fertile.The relationship between Rab39b gene deletion and PD was preliminarily studied.Including:the preliminary behavioral and electrophysiological studies of mice with Rab39b gene deletion;the detection of the expression of RAB39B protein;and the effects of Rab39b gene deletion on autophagy and mitochondrial function.Through the preliminary study in this paper,we found that in this study,compared with the normal control group,we found that the mice with Rab39b gene deletion had impaired working memory and balance ability,as well as neurosynaptic dysfunction.It is suggested that the deletion of Rab39b gene in PD may lead to progressive behavioral abnormalities associated with PD.In addition,we found that the levels of LC3B-II in male and female Rab39b knockout mice at 2 months old were significantly higher than those in wild control mice,suggesting that autophagy was changed in these mice.In the neurotoxic damage induced by MPTP,it was found that the neurotoxicity induced by MPTP was affected by the intervention of RAB39B,and that the markers of PINK1 and PARKIN,which were closely related to mitochondrial function,were also affected.It suggests that Rab39b may play an important role in maintaining mitochondrial function and participating in autophagy.These results provide clues for further study of the role of Rab39b in Parkinson's disease.