Biochemical characteristics of hereditary forms of synucleinopathies

Abstract

Parkinson’s disease (PD) and multiple system atrophy (MSA) belong to a group of synucleinopathies, the pathogenesis of which is based on the aggregation of the alpha-synuclein protein. Mutations in the LRRK2 and GBA1 genes are the most common cause of the development of hereditary forms of PD. In the present study, we estimated the frequencies of mutations in the LRRK2 (G2019S, R1441C) and GBA1 (N370S, L444P, E326K, T369M) genes among 1564 patients with PD, 117 patients with MSA and 400 control individuals in the North-West region of Russia. The level of alpha-synuclein in peripheral blood erythrocytes of patients with PD, MSA, patients with these pathologies who are carriers of mutations in the GBA1 gene, as well as control individuals was assessed. The study showed that mutations in the GBA1 gene are associated with an increased risk of developing PD and MSA, and patients with GBA1-associated PD are characterized by an increased level of total alpha-synuclein in peripheral blood erythrocytes.