Research Paper Volume 11, Issue 13 pp 4597—4610
Role of microtubule-associated protein 6 glycosylated with Gal-(β-1,3)-GalNAc in Parkinson's disease
- 1 Department of Epidemiology, Dalian Medical University, Dalian 116044, China
- 2 Biochemistry and Molecular Biology Department of College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China
- 3 Medical Administration Department, Affiliated Hospital of Jining Medical University, Jining 272000, China
received: April 3, 2019 ; accepted: June 28, 2019 ; published: July 9, 2019 ;https://doi.org/10.18632/aging.102072
How to Cite
Copyright: Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Aberrant glycosylation of proteins has major implications for human diseases. To determine whether protein glycosylation contributes to the pathogenesis of Parkinson’s disease (PD), a mouse model of PD was established by injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Induction of PD-like features was verified by assessing motor impairment and confirming reductions in biological markers, including dopamine, 5-hydroxytryptamine and tyrosine hydroxylase, as well as the aggregation of α-synuclein. Altered glycosylation was detected using biotinylated agaracus bisporus lectin, which specifically binds exposed Gal-(β-1,3)-GalNAc linked to glycoproteins. Subsequent lectin affinity chromatography coupled with mass spectrometry revealed enhanced glycosylation of microtubule-associated protein 6 (MAP6) in PD mice as compared to healthy controls. In situ dual co-immunofluorescence analysis and immunoblotting confirmed that MAP6 is glycosylated with Gal-(β-1,3)-GalNAc oligosaccharides, which in turn alters the distribution and structure of MAP6 complexes within neurons. This is the first study to described MAP6 as a glycoprotein containing Gal-(β-1,3)-GalNAc oligosaccharides and to show that hyperglycosylation of MAP6 is strongly associated with the pathogenesis of PD. These findings provide potentially valuable information for developing new therapeutic targets for the treatment of PD as well as reliably prognostic biomarkers.