Analysis of α-synuclein levels related to LRRK2 kinase activity: from substantia nigra to urine of patients with Parkinson's disease. Issue 1 (2nd January 2021)

• Record Type: Journal Article
• Authors: Nam, Daleum; Kim, Ami; Han, Sun Jung; Lee, Sung-Ik; Park, Sung-Hye; Seol, Wongi; Son, Ilhong; Ho, Dong Hwan
• Is Part Of: Animal cells and systems. Volume 25:Issue 1(2021)
• Page Start: 28
• Page End: 36
• Publication Date: 2021-01-02
• Subjects: Parkinson's disease -- α-synuclein -- leucine-rich repeat kinase 2 -- ELISA; Systems biology -- Periodicals; Biology -- Periodicals; Cytology -- Periodicals; Zoology -- Periodicals; 590
• DOI: 10.1080/19768354.2021.1883735
• Languages: English
• ISSNs: 1976-8354

Abstract

ABSTRACT: Research on Parkinson's disease (PD) has been focused on the development of PD diagnostic tools as much as the development of PD therapeutics. Several genetic culprits of PD, including DJ-1, Leucine-rich repeat kinase 2 (LRRK2), and α-synuclein (α-syn), have been investigated as markers of PD in human biofluids. Unfortunately, the approaches to develop PD diagnostic tools are impractical, and there is a considerable demand for an appropriate marker of PD. The measurement of α-syn in biofluids has recently been made more accurate by examining monomers and aggregates separately using enzyme-linked immunosorbent assay (ELISA). Previously, we reported on the development of two types of sandwich ELISA for total α-syn and MJFR-14-6-4-2 antibody-specific α-syn fibrillar oligomers. The pathogenic LRRK2 G2019S mutation is related to increased α-syn secretion in the extracellular space. We tested our established ELISA using differentiated SH-SH5Y cells transfected with LRRK2 G2019S. The secretory levels of fibrillar oligomeric α-syn divided by total α-syn were significantly increased in LRRK2 G2019S-expressing cells. Additionally, substantia nigra lysates or concentrated urine from PD patients and non-PD subjects were analyzed. We observed ambiguous changes in the levels of total or fibrillar oligomeric α-syn and their ratio between PD and non-PD. Despite the insignificant increase in the relative levels of fibrillar oligomeric α-syn to total α-syn in PD, the duration of disease progression after diagnosis significantly corresponded to the relative levels of fibrillar oligomeric α-syn to total α-syn in the urine. These results might provide greater understanding for the next stage of development of α-syn ELISAs.