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α-Synuclein Overexpression in SH-SY5Y Human Neuroblastoma Cells Leads to the Accumulation of Thioflavin S-positive Aggregates and Impairment of Glycolysis

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Abstract

Deterioration of energy metabolism in affected cells is an important feature of synucleinopathies, including Parkinson's disease. Here, we studied the association between α-synuclein accumulation and glycolysis using SH-SY5Y neuroblastoma cell lines stably expressing wild-type α-synuclein or its A53T mutant linked to the autosomal dominant form of the disease. Overexpression of both proteins led to the accumulation of thioflavin S-positive aggregates, more pronounced for α-synuclein A53T. It also caused changes in the cell energy metabolism manifested as a decrease in the lactate accumulation and glucose uptake. Impairments in glycolysis were also accompanied by a decrease in the activity of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In vitro experiments with purified proteins indicated that GAPDH inactivation might be caused by its binding to the monomeric and oligomeric forms of α-synuclein. Therefore, a decrease in the GAPDH activity induced by its interaction with α-synuclein, might be one of the causes of glucose metabolism deterioration in synucleinopathies.

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Abbreviations

α-synWT:

α-synuclein wild-type

α-synA53T:

α-synuclein A53T

CD:

circular dichroism

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

hGAPDH:

recombinant human GAPDH

G3P:

glyceraldehyde-3-phosphate

PBS:

phosphate buffered saline, pH 7.4

PD:

Parkinson’s disease

ThS:

thioflavin S

ThT:

thioflavin

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Funding

The work was supported by the Russian Foundation for Basic Research (project No. 18-34-00132).

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Authors and Affiliations

  1. Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, 119234, Moscow, Russia

    A. Melnikova & V. I. Muronetz

  2. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234, Moscow, Russia

    D. Pozdyshev, K. Barinova, S. Kudryavtseva & V. I. Muronetz

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  1. A. Melnikova
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  2. D. Pozdyshev
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  3. K. Barinova
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Correspondence to A. Melnikova.

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This article does not contain descriptions of studies with participation of humans or animals performed by any of the authors. The authors declare no conflict of interest.

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Melnikova, A., Pozdyshev, D., Barinova, K. et al. α-Synuclein Overexpression in SH-SY5Y Human Neuroblastoma Cells Leads to the Accumulation of Thioflavin S-positive Aggregates and Impairment of Glycolysis. Biochemistry Moscow 85, 604–613 (2020). https://doi.org/10.1134/S0006297920050090

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