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N-acetylcysteine increases dopamine release and prevents the deleterious effects of 6-OHDA on the expression of VMAT2, α-synuclein, and tyrosine hydroxylase
Umeå University, Faculty of Medicine, Department of Medical and Translational Biology.ORCID iD: 0000-0001-5225-0595
Umeå University, Faculty of Medicine, Department of Medical and Translational Biology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
Umeå University, Faculty of Medicine, Department of Medical and Translational Biology.
2024 (English)In: Neurological Research, ISSN 0161-6412, E-ISSN 1743-1328, Vol. 46, no 5, p. 406-415Article in journal (Refereed) Published
Abstract [en]

Objectives: Current treatments for Parkinson’s disease using pharmacological approaches alleviate motor symptoms but do not prevent neuronal loss or dysregulation of dopamine neurotransmission. In this article, we have explored the molecular mechanisms underlying the neuroprotective effect of the antioxidant N-acetylcysteine (NAC) on the damaged dopamine system.

Methods: SH-SY5Y cells were differentiated towards a dopaminergic phenotype and exposed to 6-hydroxydopamine (6-OHDA) to establish an in vitro model of Parkinson’s disease. We examined the potential of NAC to restore the pathological effects of 6-OHDA on cell survival, dopamine synthesis as well as on key proteins regulating dopamine metabolism. Specifically, we evaluated gene- and protein expression of tyrosine hydroxylase (TH), vesicle monoamine transporter 2 (VMAT2), and α-synuclein, by using qPCR and Western blot techniques. Moreover, we quantified the effect of NAC on total dopamine levels using a dopamine ELISA assay.

Results: Our results indicate that NAC has a neuroprotective role in SH-SY5Y cells exposed to 6-OHDA by maintaining cell proliferation and decreasing apoptosis. Additionally, we demonstrated that NAC treatment increases dopamine release and protects SH-SY5Y cells against 6-OHDA dysregulations on the proteins TH, VMAT2, and α-synuclein.

Conclusions: Our findings contribute to the validation of compounds capable to restore dopamine homeostasis and shed light on the metabolic pathways that could be targeted to normalize dopamine turnover. Furthermore, our results highlight the effectiveness of the antioxidant NAC in the prevention of dopaminergic neurodegeneration in the present model.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2024. Vol. 46, no 5, p. 406-415
Keywords [en]
Parkinson’s disease, N-acetylcysteine, SH-SY5Y cells, 6-OHDA, α-synuclein, VMAT2
National Category
Neurology
Identifiers
URN: urn:nbn:se:umu:diva-222487DOI: 10.1080/01616412.2024.2325312ISI: 001187198700001PubMedID: 38498979Scopus ID: 2-s2.0-85188455120OAI: oai:DiVA.org:umu-222487DiVA, id: diva2:1845597
Funder
Lars Hierta Memorial FoundationÅhlén-stiftelsenRegion VästerbottenAvailable from: 2024-03-19 Created: 2024-03-19 Last updated: 2024-05-13Bibliographically approved

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El-Habta, Roineaf Bjerkén, SaraVirel, Ana

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