Homer1a protects against neuronal injury via PI3K/AKT/mTOR signaling pathway.

Purpose: Homer1a is a member of the post-synaptic density protein family that plays an important role in neuronal synaptic activity and is extensively involved in neurological disorders. The aim of this study is to investigate the role of Homer1a in modulating neuronal survival using an in vitro traumatic neuronal injury model.Materials and methods: Neurons were extracted from rats and identifited. Then, the cells were treated with Homerla overexpression or interference vectors. Western blot was performed to evaluate the expression of Homerla, apoptosis-related proteins(caspase3, caspase8, caspase9, Fasl, Bax, and p53), autophagy-related proteins (LC3ll and Beclin1), and the activiation of PI3K/AKT/mTOM pathway. In addition, the cell viability and apoptosis rate were measured. Results: After transfection with overexpression or interference vectors, the mRNA and protein expression of Homer1a increased or decreased significantly, respectively. Upregulation of Homer1a significantly alleviated apoptosis and enhanced cell viability and autophagy after traumatic neuronal injury. Homer1a overexpression also significantly decreased the expression of the pro-apoptosis proteins caspase 3, caspase 8, caspase 9, Fasl, Bax, and p53 in neurons. Furthermore, neuron autophagy was increased after traumatic neuronal injury as demonstrated by the greater accumulation of autophagosomes and higher expression of LC3II and Beclin1 induced by Homer1a overexpression. In addition, Homer1a overexpression inhibited the activation of PI3K/AKT/mTOR signaling. Conclusion: These findings indicated that Homer1a potentially protects neurons from traumatic injury by regulating apoptosis and autophagy via the caspase and PI3K/AKT/mTOR signaling pathways and may be an effective intervention target in traumatic brain injury.

Citation

Yuan Wang, MingMing Zhao, Lv Shang, Yanguo Zhang, Conggang Huang, Zhuqiang He, Ming Luo, Bin Wu, Ping Song, Mengyang Wang, Faliang Duan. Homer1a protects against neuronal injury via PI3K/AKT/mTOR signaling pathway. The International journal of neuroscience. 2020 Jun;130(6):621-630

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PMID: 32013638

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