2Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
* To whom correspondence should be addressed.
Received February 17, 2020; Revised March 13, 2020; Accepted March 25, 2020
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.
KEY WORDS: α-synuclein, glyceraldehyde-3-phosphate dehydrogenase, glycolysis, Parkinson’s disease