Renin-Angiotensin-System Increases Phosphorylated Tau and Reactive Oxygen Species in Human Cortical Neuron Cell Line

Published: 10 June 2022| Version 1 | DOI: 10.17632/pvypjx48mv.1
Yaritza Inostroza-Nieves


Alzheimer's Disease (AD) is the most common cause of dementia. AD patients had increased ex-tracellular amyloid β plaques and intracellular hyperphosphorylated tau (p-tau) in neurons. Re-cent studies have shown an association between the Renin-Angiotensin System (RAS) and AD. The involvement of RAS has been mediated through Angiotensin II (Ang II), which is overex-pressed in aging brains. However, the exact mechanism of how Ang II contributes to AD is un-known. Thus, we hypothesize that Ang II increases p-tau by activating its kinases, CDK5 and MAPK, and in-creases the production of Reactive Oxygen Species (ROS). In the human cortical neuron cell line, HCN2, treatment with Ang II upregulated the gene expression of CDK5 (2.9 folds, p<0.0001) and MAPTK (1.9 folds, p<0.001). The AT1R antagonist, Losartan, blocked the changes in tau kinases. Also, Ang II-induced the MAPK activation, increasing its phosphorylation by 400% (p<0.0001), an increase that was also blocked by Losartan. An increase in p-tau by Ang II was ob-served using fluorescent microscopy. We then quantified ROS production, and it was significantly increased by Ang II (p<0.01), and treatment with Losartan blunted their production (p<0.05). The data obtained demonstrated that Ang II might contribute to the pathogenesis of AD.



San Juan Bautista School of Medicine


Renin-Angiotensin System, Reactive Oxygen Species, Tau, Neuro-Inflammation