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The Associations between Immunological Reactivity to the Haptenation of Unconjugated Bisphenol A to Albumin and Protein Disulfide Isomerase with Alpha-Synuclein Antibodies

1
Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA
2
TRANSCEND Research Laboratory, Department of Neurology, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129, USA
3
Department of Preventive Medicine, Loma Linda University School of Medicine, 24785 Stewart Street, Loma Linda, CA 92354, USA
4
Immunosciences Lab., Inc., 822 S. Robertson Boulevard, Suite 312, Los Angeles, CA 90035, USA
*
Author to whom correspondence should be addressed.
Toxics 2019, 7(2), 26; https://doi.org/10.3390/toxics7020026
Received: 18 March 2019 / Revised: 30 April 2019 / Accepted: 2 May 2019 / Published: 6 May 2019
(This article belongs to the Special Issue Dietary Toxicants and Neurological Disease)
Patients with Parkinson’s disease (PD) have increased susceptibility to bisphenol A (BPA) exposure since they have an impaired biotransformation capacity to metabolize BPA. PD subjects have reduced levels of conjugated BPA compared to controls. Reduced ability to conjugate BPA provides increased opportunity for unconjugated BPA to bind to albumin in human serum and protein disulfide isomerase on neurons. Once unconjugated BPA binds to proteins, it changes the allosteric structure of the newly configured protein leading to protein misfolding and the ability of the newly configured protein to act as a neoantigen. Once this neoantigen is formed, the immune system produces antibodies against it. The goal of our research was to investigate associations between unconjugated BPA bound to human serum albumin (BPA–HSA) antibodies and alpha-synuclein antibodies and between Protein Disulfide Isomerase (PDI) antibodies and alpha-synuclein antibodies. Enzyme–linked immunosorbent assay was used to determine the occurrences of alpha-synuclein antibodies, antibodies to BPA–HSA adducts, and PDI antibodies in the sera of blood donors. Subjects that exhibited high levels of unconjugated BPA–HSA antibodies or PDI antibodies had correlations and substantial risk for also exhibiting high levels of alpha-synuclein antibodies (p < 0.0001). We conclude that there are significant associations and risks between antibodies to BPA–HSA adducts and PDI antibodies for developing alpha-synuclein antibodies. View Full-Text
Keywords: bisphenol A; protein disulfide isomerase; alpha-synuclein antibodies; Parkinson’s disease; neurotoxicity bisphenol A; protein disulfide isomerase; alpha-synuclein antibodies; Parkinson’s disease; neurotoxicity
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Kharrazian, D.; Herbert, M.; Vojdani, A. The Associations between Immunological Reactivity to the Haptenation of Unconjugated Bisphenol A to Albumin and Protein Disulfide Isomerase with Alpha-Synuclein Antibodies. Toxics 2019, 7, 26.

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