ATP-γ-S-(α,β-CH2) protects against oxidative stress and amyloid beta toxicity in neuronal culture

Ortal Danino, Shlomo Grossman, Bilha Fischer

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7 Scopus citations


Amyloid beta (Aβ) oligomers and oxidative stress, typical of Alzheimer's disease, are highly neurotoxic. Previously we identified ATP-γ-S as a most promising antioxidant and neuroprotectant. To further improve both potency and metabolic stability of ATP-γ-S, we designed a related analogue, ATP-γ-S-(α,β-CH2). We found that ATP-γ-S-(α,β-CH2) effectively inhibited ROS formation in PC12 cells subjected to Fe(II)-oxidation, slightly better than ATP-γ-S (IC50 0.18 and 0.20 μM, respectively). Moreover, ATP-γ-S-(α,β-CH2) rescued primary neurons from Aβ42 toxicity, 4-fold more potently than ATP-γ-S, (IC50 0.2 and 0.8 μM, respectively). In addition, the metabolic stability of ATP-γ-S-(α,β-CH2) in PC12 cells during 4 h of incubation, was up to 20% greater than that of ATP-γ-S and ATP. Previously, we found that ATP-γ-S-(α,β-CH2) resisted hydrolysis by ecto-nucleotidases such as, NPPs and TNAP, and was found to be ∼7-fold more potent agonist than ATP at P2Y11 receptor. Therefore, we propose ATP-γ-S-(α,β-CH2) as a promising agent for rescue of neurons from insults typical of Alzheimer's disease.

Original languageEnglish
Pages (from-to)446-450
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - 1 May 2015

Bibliographical note

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© 2015 Elsevier Inc. All rights reserved.


  • Amyloid beta
  • Antioxidant
  • Neuroprotectant
  • Nucleotide


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