eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
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vol. 62
Original paper

LMTK2 inhibits Ab25-35-elicited ferroptosis, oxidative stress and apoptotic damage in PC12 cells through activating Nrf2/ARE signalling pathway

Lili Zhang
Fei Shu

  1. Department of Psychiatry, Zutangshan Hospital, Nanjing, China
  2. Department of Psychiatry, Nanjing Brain Hospital, Nanjing, China
Folia Neuropathol 2024; 62 (1): 47-58
Online publish date: 2023/12/08
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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 Ab25-35 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, Fe2+ 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 Ab25-35-treated PC12 cells. Notably, LMTK2 overexpression exhibited inhibitory effects on oxidative stress, apoptosis and ferroptosis in PC12 cells exposed to Ab25-35. The upregulated Nrf2, NQO1 and HO-1 expressions in LMTK2 overexpressed-PC12 cells with Ab25-35 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 Ab25-35-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 Ab25-35 through the activation of the Nrf2/ARE signalling pathway, indicating the potential target of LMTK2 in the treatment of AD.

Alzheimer’s disease, LMTK2, ferroptosis, oxidative stress, apoptotic damage, Nrf2/ARE signalling pathway

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