@Article{Zhang2024,
journal="Folia Neuropathologica",
issn="1641-4640",
volume="62",
number="1",
year="2024",
title="LMTK2 inhibits Ab25-35-elicited ferroptosis, oxidative stress and apoptotic damage in PC12 cells through activating Nrf2/ARE signalling pathway",
abstract="Alzheimer’s disease (AD), the most common contributor to dementia, is a growing global health problem. This study aimed to investigate the role of lemur tyrosine kinase 2 (LMTK2) in AD as well as its relevant mechanism. To establish an in vitro cell model, PC12 cells were challenged with 20 µmol/l Ab 25-35  for 24 h. RT-qPCR and western blot examined LMTK2 mRNA and protein expressions. With the application of CCK-8, TUNEL, iron colorimetric assay kit and DCFH-DA, the viability, apoptosis, Fe 2+  and ROS content in PC12 cells were assessed. Besides, the expressions of oxidative stress-, apoptosis-, ferroptosis- and Nrf2/ARE signalling-related proteins were evaluated with western blot. Moreover, commercial kits examined SOD, MDA and CAT contents. The results manifested that LMTK2 expression was noticeably downregulated in Ab 25-35 -treated PC12 cells. Notably, LMTK2 overexpression exhibited inhibitory effects on oxidative stress, apoptosis and ferroptosis in PC12 cells exposed to Ab 25-35 . The upregulated Nrf2, NQO1 and HO-1 expressions in LMTK2 overexpressed-PC12 cells with Ab 25-35  induction revealed that LMTK2 overexpression could activate the Nrf2/ARE signalling pathway. What is more, a series of cellular experiments further testified that ML385, a specific Nrf2 inhibitor, partly hindered the protective role of LMTK2 overexpression against Ab 25-35 -triggered oxidative stress, apoptosis and ferroptosis in PC12 cells. In conclusion, LMTK2 overexpression alleviated the ferroptosis, oxidant damage and apoptosis in PC12 cells exposed to Ab 25-35  through the activation of the Nrf2/ARE signalling pathway, indicating the potential target of LMTK2 in the treatment of AD.",
author="Zhang, Lili
and Shu, Fei",
pages="47--58",
doi="10.5114/fn.2023.133472",
url="http://dx.doi.org/10.5114/fn.2023.133472"
}