Biological Effects Of Retinoic Acid And AuNPs In Cell Models Of Neurodegenerative Diseases

Neurodegenerative diseases are serious threats to human health,of which the pathogenic hypothesises include free radical damage,neuroinflammatory response,and abnormal protein aggregation.Based on the pathogenic hypothesis,the therapeutic drugs for neurodegenerative diseases are classified into antioxidants,anti-inflammatory drugs and anti-aggregation agents,but no drug can reverse the progress of the disease.Therefore,the development of drugs needs further research.Recently,natural products have been used for the treatment of neurodegenerative diseases because of their multiple targets and few adverse reactions.Furthermore,nanomaterials have good permeability,targeting and controlled release,and have been used in clinical treatment of cancer and vascular diseases.In this paper,retinoic acid?RA?and gold nanoparticles?AuNPs?were co-cultured respectively with cell models of neurodegenerative diseases to explore their biological effects,to provide new ideas for the treatment of diseases and to reveal the neurotoxicity of drugs.The detailed experimental studies and main results are as follows:?1?Cell models were constructed including Alzheimer's disease?AD?cell model,Parkinson's disease?PD?cell model,oxidative damage cell model,glaucoma cell model,and excitotoxic cell model.RA and AuNPs were co-cultured with cell models,respectively.The results of CCK-8 assay showed that RA with concentration less than10?M was non-toxic,accelerated the apoptosis of SH-SY5Y cells induced by?-amyloid?A??,and decreased the damage of SH-SY5Y cells induced by MPP⁺.However,it has no obvious effect on oxidative damage and excitotoxic damage.AuNPs with concentration less than 100 mg·L^-1 were non-toxic and could significantly synergize with sodium nitroprusside?SNP?to damage RGC-5 cells,could significantly increase the viability of AD and PD model cells,but had no significant effect on oxidative damage and excitotoxic damage.?2?The mechanism that RA cooperates with A?40 to damage SH-SY5Y cells was explored.The results showed that RA could significantly inhibit A?40 fibrillation and affect the transformation of A?40 through ThT fluorescence,atomic force microscopy?AFM?,dynamic light scattering and circular dichroism.RA could significantly induce reactive oxygen species?ROS?and nitric oxide?NO?in AD model cells by fluorescent probes.A series of experiments had shown that RA inhibited A?40 monomer fibrillation,which increased the content of high-toxic A?oligomers and protofibrils,resulting in increased intracellular ROS and NO levels,induced oxidative damage and ultimately accelerated apoptosis.?3?The mechanism that AuNPs synergize with SNPs to damage RGC-5 cells was studied.The results showed that with the synergy of 10 mg·L^-1 AuNPs,SNP induced cell damage by 80 times.The field emission scanning electron microscope and transmission electron microscopy showed that AuNPs could change the cell morphology and were metabolized in the cells to produce spheres with a diameter of about 500 nm.Fluorescence probes and Western blot experiments showed that AuNPs increased the levels of ROS,NO,p-TRKB and p-ERK in glaucoma model cells.The above experimental results showed that AuNPs could change the cell morphology,resulting in decreased tolerance of cells to low concentrations of SNP,increased intracellular ROS and NO content,disrupted the oxidation-antioxidant system balance,induced oxidative damage,and simultaneously MAPK signals was also activated,triggering a cascade of reactions,ultimately lead to apoptosis.