Aggregation of α-synuclein in brain samples from subjects with glucocerebrosidase mutations.

Abstract

Recent studies show an increased frequency of mutations in the glucocerebrosidase gene (GBA1) in patients with α-synucleinopathies including Parkinson disease. Some patients with Gaucher disease (GD) develop parkinsonism with α-synuclein-positive inclusions post mortem. Proteins were extracted from the cerebral cortex of subjects with synucleinopathies with and without GBA1 mutations, controls and patients with GD. Patients with GBA1-associated synucleinopathies showed aggregation of oligomeric forms of α-synuclein in the SDS-soluble fraction, while only monomeric forms of α-synuclein were seen in subjects with GBA1 mutations without parkinsonism. Thus, brains from patients with GBA1-associated parkinsonism show biochemical characteristics typical of Lewy body disorders.

• Authors: Jae Hyuk Choi, Barbara Stubblefield, Mark R Cookson, Ehud Goldin, Arash Velayati, Nahid Tayebi, Ellen Sidransky
• Journal: Molecular genetics and metabolism (Mol Genet Metab) 2011 Sep-Oct Vol. 104 Issue 1-2 Pg. 185-8 ISSN: 1096-7206 [Electronic] United States
• PMID: 21742527 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• alpha-Synuclein
• Glucosylceramidase

Topics

• Adult
• Aged
• Aged, 80 and over
• Brain (metabolism, pathology)
• Female
• Glucosylceramidase (genetics)
• Humans
• Male
• Middle Aged
• Mutation (genetics)
• Protein Structure, Quaternary
• Solubility
• alpha-Synuclein (chemistry, metabolism)