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. 2011 Sep-Oct;104(1-2):185-8.
doi: 10.1016/j.ymgme.2011.06.008. Epub 2011 Jun 17.

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

Jae Hyuk Choi  1 , Barbara Stubblefield, Mark R Cookson, Ehud Goldin, Arash Velayati, Nahid Tayebi, Ellen Sidransky
Affiliations

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

Jae Hyuk Choi et al. Mol Genet Metab. 2011 Sep-Oct.

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.

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Figures

Fig. 1
Fig. 1
Solubility and aggregation of α-synuclein in brain (A, B and C). Brain samples from neurologically normal control subjects (#1–7), patients with synucleinopathies (#8–13), patients with GD and carriers of GBA1 mutations exhibiting synucleinopathies (#14–23), and patients with GD (#24–30) were fractionated by solubility. Tris-buffered saline (TBS)-soluble (panel A), sodium dodecyl sulfate (SDS)-soluble (panel B), and urea-soluble (panel C) fractions were blotted for α-synuclein using monoclonal Syn-1. Arrow indicates the major band of monomeric α-synuclein (17 kDa); asterisk indicates oligomeric α-synuclein. The SDS-soluble fraction was additionally blotted with anti-glucocerebrosidase antibody (R386). GCase is shown as a single band at 60 kDa. (panel D). Blots were reprobed with β-actin to assess loading (panels below each figure).
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References

    1. Lwin A, Orvisky E, Goker-Alpan O, LaMarca ME, Sidransky E. Glucocerebrosidase mutations in subjects with parkinsonism. Mol Genet Metab. 2004;81:70–73. - PubMed
    1. Tayebi N, Walker J, Stubblefield B, Orvisky E, LaMarca ME, Wong K, Rosenbaum H, Schiffmann R, Bembi B, Sidransky E. Gaucher disease with parkinsonian manifestations: does glucocerebrosidase deficiency contribute to a vulnerability to parkinsonism? Mol Genet Metab. 2003;79:104–109. - PubMed
    1. Wong K, Sidransky E, Verma A, Mixon T, Sandberg GD, Wakefield LK, Morrison A, Lwin A, Colegial C, Allman JM, Schiffmann R. Neuropathology provides clues to the pathophysiology of Gaucher disease. Mol Genet Metab. 2004;82:192–207. - PubMed
    1. Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R. Mutations in the glucocerebrosidase gene and Parkinson’s disease in Ashkenazi Jews. N Engl J Med. 2004;351:1972–1977. - PubMed
    1. Clark LN, Kartsaklis LA, Wolf Gilbert R, Dorado B, Ross BM, Kisselev S, Verbitsky M, Mejia-Santana H, Cote LJ, Andrews H, Vonsattel JP, Fahn S, Mayeux R, Honig LS, Marder K. Association of glucocerebrosidase mutations with dementia with lewy bodies. Arch Neurol. 2009;66:578–583. - PMC - PubMed

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