Ladostigil attenuates induced oxidative stress in human neuroblast-like sh-sy5y cells

Keren Zohar, Elyad Lezmi, Tsiona Eliyahu, Michal Linial*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


A hallmark of the aging brain is the robust inflammation mediated by microglial ac-tivation. Pathophysiology of common neurodegenerative diseases involves oxidative stress and neuroinflammation. Chronic treatment of aging rats by ladostigil, a compound with antioxidant and anti-inflammatory function, prevented microglial activation and learning deficits. In this study, we further investigate the effect of ladostigil on undifferentiated SH-SY5Y cells. We show that SH-SY5Y cells exposed to acute (by H2 O2) or chronic oxidative stress (by Sin1, 3-morpholinosydnonimine) induced apoptotic cell death. However, in the presence of ladostigil, the decline in cell viability and the increase of oxidative levels were partially reversed. RNA-seq analysis showed that prolonged oxidation by Sin1 resulted in a simultaneous reduction of the expression level of endoplasmic reticu-lum (ER) genes that participate in proteostasis. By comparing the differential gene expression profile of Sin1 treated cells to cells incubated with ladostigil before being exposed to Sin1, we observed an over-expression of Clk1 (Cdc2-like kinase 1) which was implicated in psychophysiological stress in mice and Alzheimer’s disease. Ladostigil also suppressed the expression of Ccpg1 (Cell cycle progression 1) and Synj1 (Synaptojanin 1) that are involved in ER-autophagy and endocytic pathways. We postulate that ladostigil alleviated cell damage induced by oxidation. Therefore, under conditions of chronic stress that are observed in the aging brain, ladostigil may block oxidative stress processes and consequently reduce neurotoxicity.

Original languageAmerican English
Article number1251
Issue number9
StatePublished - 17 Sep 2021

Bibliographical note

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© 2021 by the authorsLicensee MDPI, Basel, Switzerland.


  • Alzheimer’s disease
  • ER stress
  • Microglial activation
  • Mitophagy
  • Neurodegenerative disease
  • RNA-seq
  • UPR


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