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OPTN attenuates the neurotoxicity of abnormal Tau protein by restoring autophagy
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AbstractOPTN is an autophagy receptor involved in autophagic degradation. Here we studied the role of OPTN in attenuating the neurotoxicity induced by mutated Tau protein. We constructed recombinant adeno-associated viruses with OPTN and Tau-P301L genes, respectively. Through virus coinfection on neuronal cell line HT22 in vitro and Kunming mice in vivo, we found that autophagy- and apoptosis-associated genes are altered by Tau-P301L at both mRNA and protein levels, which are restored by OPTN expression. Functionally, OPTN suppresses apoptosis and enhances cellular viability in Tau-P301L expressing HT22 cells, and increases learning and memory in Tau-P301L expressing mice, respectively. Last, we found that OPTN reduces the p-Tau levels in vitro and in vivo. Our results reveal the function of OPTN in lowering the p-Tau level and the expressions of apoptosis genes, and increasing the expressions of autophagic genes, indicating a beneficial role of OPTN in Tau pathology.
Springer Science and Business Media LLC
Title: OPTN attenuates the neurotoxicity of abnormal Tau protein by restoring autophagy
Description:
AbstractOPTN is an autophagy receptor involved in autophagic degradation.
Here we studied the role of OPTN in attenuating the neurotoxicity induced by mutated Tau protein.
We constructed recombinant adeno-associated viruses with OPTN and Tau-P301L genes, respectively.
Through virus coinfection on neuronal cell line HT22 in vitro and Kunming mice in vivo, we found that autophagy- and apoptosis-associated genes are altered by Tau-P301L at both mRNA and protein levels, which are restored by OPTN expression.
Functionally, OPTN suppresses apoptosis and enhances cellular viability in Tau-P301L expressing HT22 cells, and increases learning and memory in Tau-P301L expressing mice, respectively.
Last, we found that OPTN reduces the p-Tau levels in vitro and in vivo.
Our results reveal the function of OPTN in lowering the p-Tau level and the expressions of apoptosis genes, and increasing the expressions of autophagic genes, indicating a beneficial role of OPTN in Tau pathology.
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