DOI: 10.1002/alz.077820 ISSN: 1552-5260

Ameliorating amyloid beta oligomer toxicity with NAC

Ezgi Keske, Nagehan ERSOY TUNALI
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Alzheimer’s Disease (AD) has a complex neuropathology, involving diverse cellular pathways. Molecular mechanisms induced by beta‐amyloid oligomer (Aβo) toxicity are considered to be the major initiators of neuropathology. Therefore, Aβos are commonly used to mimic toxicity in AD. The primary effect of Abeta toxicity is increase in cellular oxidative stress. Likewise, recent AD drug research and preclinical trials has been focused on reducing ROS and/or increasing antioxidant capacity. N‐acetyl cysteine (NAC) is a well‐known mucolytic agent and a powerful antioxidant via increasing GSH levels. In this respect, we aimed to investigate the effect of NAC in reducing oxidative stress in Aβo‐induced cellular toxicity.


SH‐SY5Y cells were cultured in DMEM medium containing 10% FBS and 1% pen/strep. In order to establish Aβo toxicity, Aβ(1‐42) peptide was dissolved in NH4OH at various concentrations (5‐100 μM) and incubated at 4°C for 24h. Oligomer formation was verified with Bis‐ANS test and Aβo toxicity was analyzed using WST‐1. Changes in the oxidative stress levels of the cells due to Aβo toxicity and NAC was quantified using Total Oxidant/Antioxidant Capacity kits based on spectrophotometric absorbance.


Bis‐ANS test showed a linear correlation between oligomer formation and Aβo concentration. According to the cell viability assay results, 10 μM Aβ42o for 24 hrs was used to establish Aβo toxicity in vitro. At 1 and 5mM concentrations, NAC was shown to increase the viability, GSH levels and antioxidant capacity of the SH‐SY5Y cells significantly. Likewise, 1,5, and 10mM NAC was shown to reduce Aβo‐induced toxicity significantly. Furthermore, although 20 and 40mM NAC decreases viability of healthy cells, they increase viability in Aβo‐treated cells.


According to our results, NAC can be regarded as a potent molecule in ameliorating Aβo‐induced toxicity.

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