Home > Publications Database > The specific NQO2 inhibitor, S29434, only marginally improves the survival of dopamine neurons in MPTP-intoxicated mice. > print

001     266788
005     20240118114610.0
024 7 _ |a 10.1007/s00702-023-02709-3
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024 7 _ |a pmid:37851107
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024 7 _ |a 0375-9245
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024 7 _ |a 0022-3026
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024 7 _ |a 0300-9564
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024 7 _ |a 1435-1463
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037 _ _ |a DZNE-2024-00046
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Vallucci, Maeva
|0 0000-0002-9645-0553
|b 0
245 _ _ |a The specific NQO2 inhibitor, S29434, only marginally improves the survival of dopamine neurons in MPTP-intoxicated mice.
260 _ _ |a Wien [u.a.]
|c 2024
|b Springer
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Over the years, evidence has accumulated on a possible contributive role of the cytosolic quinone reductase NQO2 in models of dopamine neuron degeneration induced by parkinsonian toxin, but most of the data have been obtained in vitro. For this reason, we asked the question whether NQO2 is involved in the in vivo toxicity of MPTP, a neurotoxin classically used to model Parkinson disease-induced neurodegeneration. First, we show that NQO2 is expressed in mouse substantia nigra dopaminergic cell bodies and in human dopaminergic SH-SY5Y cells as well. A highly specific NQO2 inhibitor, S29434, was able to reduce MPTP-induced cell death in a co-culture system of SH-SY5Y cells with astrocytoma U373 cells but was inactive in SH-SY5Y monocultures. We found that S29434 only marginally prevents substantia nigra tyrosine hydroxylase+ cell loss after MPTP intoxication in vivo. The compound produced a slight increase of dopaminergic cell survival at day 7 and 21 following MPTP treatment, especially with 1.5 and 3 mg/kg dosage regimen. The rescue effect did not reach statistical significance (except for one experiment at day 7) and tended to decrease with the 4.5 mg/kg dose, at the latest time point. Despite the lack of robust protective activity of the inhibitor of NQO2 in the mouse MPTP model, we cannot rule out a possible role of the enzyme in parkinsonian degeneration, particularly because it is substantially expressed in dopaminergic neurons.
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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a MPTP
|2 Other
650 _ 7 |a NQO2
|2 Other
650 _ 7 |a Neuroprotection
|2 Other
650 _ 7 |a Parkinson disease
|2 Other
650 _ 7 |a S29434
|2 Other
650 _ 7 |a NRH - quinone oxidoreductase2
|0 EC 1.6.99.-
|2 NLM Chemicals
650 _ 7 |a N-(2-(2-methoxy-6H-dipyrido(2,3-a-3,2-e)pyrrolizin-11-yl)ethyl)-2-furamide
|2 NLM Chemicals
650 _ 7 |a Dopamine
|0 VTD58H1Z2X
|2 NLM Chemicals
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Dopaminergic Neurons: metabolism
|2 MeSH
650 _ 2 |a MPTP Poisoning
|2 MeSH
650 _ 2 |a Neuroblastoma
|2 MeSH
650 _ 2 |a Substantia Nigra: metabolism
|2 MeSH
650 _ 2 |a Dopamine: metabolism
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
700 1 _ |a Boutin, Jean A
|0 0000-0003-0068-7204
|b 1
700 1 _ |a Janda, Elzbieta
|0 0000-0002-6787-7291
|b 2
700 1 _ |a Blandel, Florence
|b 3
700 1 _ |a Musgrove, Ruth
|0 P:(DE-2719)2810507
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700 1 _ |a Di Monte, Donato
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700 1 _ |a Ferry, Gilles
|0 0000-0003-0689-7923
|b 6
700 1 _ |a Michel, Patrick P
|0 0000-0001-5607-3119
|b 7
700 1 _ |a Hirsch, Etienne C
|0 0000-0003-4823-276X
|b 8
773 _ _ |a 10.1007/s00702-023-02709-3
|g Vol. 131, no. 1, p. 1 - 11
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|p 1 - 11
|t Journal of neural transmission
|v 131
|y 2024
|x 0375-9245
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