Mechanism Study Of High Glucose On PD-related Proteins Such As α-synuclein

Background:Parkinson’s disease is a common neurodegenerative disease.In recent years,many studies have proved that Parkinson’s disease is related to diabetes.Patients with diabetes have higher risk of Parkinson’s diseases;In Parkinson patients accompanied with diabetes,the sympotmes of Parkinson are more serious than those without diabetes.However,does the parallel progress of these two diseases indicate some common pathogenesis?Which is still largely unkown.Further study on the common pathogenesis of diabetes and parkinson’s diseases may provide a new insight of the mechanisms and new direction for the treatment of the comorbidity of these two diseases.In the current research,the common causes of the two diseases are protein misfolding,mitochondrial dysfunction,inflammation,vitamin D and other factors.However,there are few studies on the specific proteins involved.In this study,we use several proteins to explore whether diabetes can induce PD through corresponding pathways:α-synuclein is a common misfolded and aggregated protein in Parkinson’s disease;the autophagy protein LC3B reflects the clearance of abnormal proteins in cells;Nurrl and Tyrosine Hydroxylase(TH)are related to the production of dopamine,and to some extent reflect the dopamine in the cell The change.Pericytes are components of the blood-brain barrier.CD 13 and Platelet-derived growth factor receptor-β(PDGFR-β)are markers of the pericytes,showing changes of the blood-brain barrier.N-ethylmaleimide sensitive factor(NSF)participates in the process of synaptic vesicle fusion,reflecting some pathophysiological changes in synapses.Method:1.Cell culture:Human neuroblastoma cells SH-SY5Y were cultured in DMEM high glucose medium to study the effect of different sugar concentrations on cell viability,and the changes in the protein content of cells such as Nurrl under different sugar concentrations and 6-OHDA treatment were measured and compared.2.Experimental animals:Three-month-old SNCA A53T mutant mice and wild-type mice were given high-sugar and high-fat diets or ordinary diets,and divideed into four groups:control group,PD group,diabetes group,and PD+diabetes group,TH and other protein content changes.Result:1.After 3 days of high concentration glucose treatment,cell viability significantly decreased.2.Under the treatment of glucose at 50 mM,Nurrl,LC3B and other proteins of the cells increased slightly,and when the concentration was 75 mM,these two proteins decreased significantly.At the same glucose concentration,the presence of 100 μM 6-OHDA had no effect on the expression of Nurrl,but reduced the expression of LC3B.Under the treatment of glucose at 50 mM,the expression of phospho-α-synuclein increased.3.In the frontal cortex of mice,diabetes significantly increased the content ofα-synuclein and significantly reduced the content of TH;in the striatum,diabetes had no significant effect on α-synuclein,which significantly increased TH.Diabetes also altered the expression of pericyte-associated proteins PDFGR-β,CD13,and NSF.Conclusion:In vitro,we showed that high glucose can reduce cell activity;high glucose also induced a decrease in Nurrl,a decrease in the autophagy protein LC3B,and increased the expression of phosphorylated α-synuclein.These changes may be involved in the pathogenesis of PD.In vivo,we further confirmed that diabetes can induce PD by increasing phosphorylated α-synuclein.At the same time,we also found that PD and diabetes altered the expression of CD 13 and PDGFR-β,suggesting that there are some changes in pericytes,which may reflects changes in blood-brain barrier.Besides,changes in NSF suggest that PD and diabetes have altered the process of synaptic vesicle fusion.