| Parkinson’s disease(PD)is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the dense part of the substantia nigra and Louis’s pathology.Louis pathology refers to the abnormal aggregation of alphasynuclein,which plays a key role in the pathophysiology of PD.The complexity of the pathogenesis of Parkinson’s disease brings great challenges to clinical treatment.Current clinical drugs cannot prevent or delay the process of neurodegenerative diseases,so it is urgent to seek new treatment methods and drugs.Natural compounds such as curcumin and trehalose have been reported to inhibit synaptic nuclein,but the therapeutic effect is not obvious.Resveratrol(RV),as a polyphenolic compound with many biological activities,has many biological functions such as heart protection,anti-inflammatory and antioxidant.Resveratrol may also protect against a variety of neurodegenerative diseases and their associated complications,new research suggests.However,the therapeutic and preventive effects of resveratrol on Parkinson’s disease and its mechanism have not been fully elucidatedBased on the above background,this study investigated the effect of resveratrol on a-synclein aggregation by ThT,TEM,MTT and other techniques.The effects of resveratrol on animal behavior,coordination and cognition were further studied by animal behavior.The levels of total a-synclein and a-synclein oligomers in the brain of transgenic mice were detected by Western,Dot blot and immunohistochemistry,and the pathological changes related to PD were detected by immunohistochemistry In addition,the effects of resveratrol on inflammatory level and oxidative stress level were verified by immunohistochemistry and ELISA,so as to reveal the mechanism of resveratrol in the treatment of Parkinson’s disease.The research results are as follows(1)By detecting the conformation and molecular level of the a-synclein oligomers,it is found that both low concentration and high concentration of resveratrol have inhibitory effects on the a-synclein oligomers,and the inhibitory effect of high concentration of resveratrol is more obvious.The cell level showed that the nerve cells are co-incubated with a-synclein,and the high dose of resveratrol significantly enhance the cell activity(2)Through field experiment,pole climbing experiment,claw-holding experiment and other animal experiments,it is found that the movement disorder of A53T transgenic mice treated with resveratrol is significantly improved;In addition,the new thing cognition and Y maze also prove that the cognitive impairment of transgenic mice is effectively alleviated.(3)According to Western and ELISA tests,resveratrol can reduce the a-synuclein level in the brain of A53T transgenic mice,and it is also verified by immunohistochemistry that the phosphorylation of Seri 29 is decreased,while the rate limiting enzyme of dopamine synthesis is significantly increased.(4)EllSA and immunohistochemical results showed that resveratrol inhibited the activation of astrocytes and microglias,and reduced the levels of inflammatory factors and reactive oxygen species in mice,thereby inhibiting the inflammatory response of transgenic mice and reducing the level of oxidative stress.Based on the above research results,we clarify the molecular mechanism of resveratrol in the treatment of Parkinson’s disease as follows:resveratrol effectively reduces the agaregation of a-synuclein.alleviates the cell death caused by the aggregation of a-synuclein,and improves the cell survival rate.Behavioral studies have shown that resveratrol improves motor impairment and cognitive impairment in transgenic mice.Meanwhile,resveratrol effectively reduced the level of total a-synuclein and oligomers.In addition,inflammatory and oxidative stress responses of transgenic mice were effectively reduced. |
PDF Full Text Request