| ObjectiveParkinson’s disease(PD)is a common neurodegenerative disease in middle-aged and elderly people.Currently,the treatment of PD is still mainly based on DA replacement therapy,which is to supplement the DA content in the brain with dopaminergic drugs,so as to improve the movement disorder of patients.However,drug treatment can only relieve the movement symptoms,but cannot prevent the development of PD,and serious side effects and significantly decreased efficacy will occur after long-term use.Therefore,seeking new therapeutic strategies is one of the research hotspots of PD.Disease-modification therapy(DMT)is the use of drugs or other methods to slow the progression of the disease so that the patient can live a longer normal life.α-lipoic acid(α-LA)has antioxidant effect and can cross the blood-brain barrier and thus have a protective effect on neurons.However,the molecular mechanism of its neuroprotective effect is not fully understood.To investigate protective effect of α-LA on neuron and mitochondria and the molecular mechanism of α-synuclein(α-syn)scavenging using the PD drosophila model.MethodsElave-GAL4>UAS-SNCA.A30 P strain drosophila was used as PD model group.The Elave-GAL4 strain drosophila was used as the control group.The PD drosophila maintained in normal medium mixed with 2.15 m M of α-LA was used as α-LA treatment group.The effects of α-LA on the climbing ability and lifespan were observed.Then,reagent test kits were used to measure the level of reactive oxygen species(ROS),glutathione(GSH),malondialdehyde(MDA),superoxide dismutase(SOD)and adenosine triphosphate(ATP).Furthermore,the protein was extrcacted from the head of drosophila,and the expression of tyrosine hydroxylase(TH),ADH dehydrogenase [ubiquinone] ferrithionein 3(NDUFS3),α-synuclein(α-syn)and autphagy related 5(Atg5),autphagy related 8a(Atg8a)were detected by Western blot.At the same time,DA neuron were detected by immunofluorescence.Resultsα-LA can successfully rescue the decrease of lifespan(P<0.05)and the loss of climbing ability in PD drosophila(P<0.0001).The α-LA could significantly decrease the level of ROS(P<0.05),MDA(P<0.05),α-syn(P<0.01)and increase the level of GSH(P<0.05),SOD(P<0.0001),ATP(P<0.01).The α-LA could promote the expression of TH(P<0.05),NDUFS3(P<0.05)and Atg5(P<0.05),Atg8a(P<0.05).α-LA could not decrease the aggregation of α-syn in PD Drosophila after the expression of Atg5 and Atg8 a was inhibited by RNAi.Conclusion1.The α-LA can effectively mitigate the dopaminergic neuron loss and mitonchondrial dyfunction on PD drosophila model.2.α-LA may promote autophagy level to degrade the aggregation α-syn. |
