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Integrin-linked kinase is a key signal factor involved in Nogo-66-induced inhibition of neurite outgrowth

By Ya-ping Yu, Qiang-ping Wang, Jian-Ying Shen, Nan-xiang Xiong, Hua Yu, Peng Fu, Lei Wang, Ye Yuan, Hong-yang Zhao, Fang-cheng Zhang, Hendrik Pool

Posted 14 Apr 2020
bioRxiv DOI: 10.1101/2020.04.14.040444

Nogo-66, the extracellular domain of Nogo-A, has been identified as the most important myelin-associated neuronal growth inhibitor. Evidence suggested that Nogo-66 exert its neurite inhibition effect via a Nogo-66/Protein kinase B (PKB)/Glycogen synthase kinase-3β (GSK-3β)/tau signaling pathway. Integrin-linked kinase (ILK) is a serine/threonine kinase mediating axon upstream growth of PKB and GSK-3β. However, the contribution of ILK to the Nogo-66-induced inhibition of neurite, is not clear. In this study, we set out to reveal the role of ILK on Nogo-66 signaling in vitro and in vivo. To deteremine this directly, Recombinant adenoviruses were constructed to upregulate or downregulate the expresioon of ILK in Neuro 2a (N2a))and analysis the change of downstream molecule and neurite length. The results showed that Nogo-66 inhibited the phosphorylation of ILK, while ILK regulated the phosphorylation of PKB and GSK-3β, and the expression of tau in Nogo-66-treated N2a cells. ILK overexpression through lentivirus vector transfection reduced the inhibitory effect of neurite outgrowth induced by Nogo-66 in cortical neurons. The Tau expression in the complete spinal cord transection rat model was promoted by the overexpression of ILK. Our findings indicated that ILK is a key signal factor involved in Nogo-66-induced inhibition of neurite outgrowth. The mechanism of Nogo-66 signaling pathway was further explained and a proper target for the promotion of neural regeneration was also provided by this study. ### Competing Interest Statement The authors have declared no competing interest.

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