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

Biochemical and Biophysical Research Communications
Ortal DaninoBilha Fischer

Abstract

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.

References

Nov 4, 2004·NMR in Biomedicine·John F Schenck, Earl A Zimmerman
May 23, 2006·Nature Reviews. Neuroscience·R Douglas Fields, Geoffrey Burnstock
Aug 10, 2006·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Yael Richter, Bilha Fischer
Apr 13, 2007·Physiological Reviews·Geoffrey Burnstock
Jul 5, 2008·Purinergic Signalling·Kenneth A JacobsonHyojin Ko
Aug 5, 2008·Combinatorial Chemistry & High Throughput Screening·Dayle HoustonT Kendall Harden
Nov 15, 2008·Trends in Neurosciences·Maria P AbbracchioHerbert Zimmermann
Jun 2, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Aviran AmirBilha Fischer
Jun 8, 2013·Nucleosides, Nucleotides & Nucleic Acids·Ortal DaninoBilha Fischer
Sep 21, 2013·Inorganic Chemistry·Alon Haim SayerBilha Fischer
Feb 20, 2014·Biochemical Pharmacology·O DaninoB Fischer

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Citations

Sep 10, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhang JunZou Yuan
Jun 3, 2021·Cells·Stefania MerighiDavide Ferrari

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