γ-Adducin Alleviates Neurite Damage Induced By Aβ_1-42 Fibrils

Objective This study aimed to explore whetherγ-Adducin alleviates neurite damage induced by Aβ_1-42 fibrils in neurons and search for novel therapeutic targets for Alzheimer’s disease.Methods Experiment#1:Primary cultured neurons were exposed to Aβ_1-42 fibrils at a concentration of 10μmol/L for 24 hours,neurite change was measured by staining with neuronal marker microtubule associated protein 2（MAP2）.Apoptosis was detected by TUNEL staining.Experiment#2:Primary neurons were pre-treated with adeno-associated virus（AAVs）encoding GFP-Vector or GFP-γ-Adducin,respectively,5 days after adeno-associated virus infection,Aβ_1-42 fibrils（10μmol/L）were added into both groups,immunofluorescence staining was performed to detect the effect ofγ-Adducin on neurite damage induced by Aβ_1-42fibrils.Dil staining was used to detect the changes of dendritic spines density in primary neurons.Results The neurite of control group grew well.The morphology of the neurite was continuous and complete,whereas the neurons showed significant neurite damage after treated with 10μmol/L Aβ_1-42 fibrils,indicating Aβ_1-42 fibrils induce damage of neurites.In order to clarify the effect of Aβ_1-42 fibrils on neuron,TUNEL staining was used to illustrate neuronal apoptosis.We found that neurons treated with Aβ_1-42 fibrils showed increased apoptosis compared to control group.To further clarify the effect ofγ-Adducin on the morphology of neuronal processes and neuronal apoptosis,we infected neurons with AAVs encoding GFP-Vector or GFP-γ-Adducin,respectively,and then treated the neurons with Aβ_1-42 fibrils.We found that neurons expressing GFP-γ-Adducin had a lower proportion of abnormal neuronal processes and lower apoptosis compared to the GFP-Vector control group.Besides,Dil staining showed that the densities of dendritic spines in the GFP-γ-Adducin treated group was much higher than those in the GFP-Vector control group.Conclusion Our results indicate thatγ-Adducin alleviates neuronal neurite damage induced by Aβ_1-42 fibrils.This protective mechanism may be the related to the axon guidance signal pathway.γ-Adducin may be a novel therapeutic target for Alzheimer’s disease.