干旱区生态环境知识资源中心(Arid): Chemoselective Bioconjugation of Amyloidogenic Protein Antigens to PEGylated Microspheres Enables Detection of alpha-Synuclein Autoantibodies in Human Plasma

Arid

DOI	10.1021/acs.bioconjchem.1c00530
	Chemoselective Bioconjugation of Amyloidogenic Protein Antigens to PEGylated Microspheres Enables Detection of alpha-Synuclein Autoantibodies in Human Plasma
	Ge, Peng; Yang, Mu; Bouchard, Jacob L.; Dzamko, Nicolas; Lewis, Simon J. G.; Halliday, Glenda M.; Doran, Todd M.
通讯作者	Ge, P
来源期刊	BIOCONJUGATE CHEMISTRY
ISSN	1043-1802
EISSN	1520-4812
出版年	2022
卷号	33 期号:2 页码:301-310
英文摘要	The misfolding and subsequent aggregation of amyloidogenic proteins is a classic pathological hallmark of neurodegenerative diseases. Aggregates of the alpha-synuclein protein (alpha S) are implicated in Parkinson's disease (PD) pathogenesis, and naturally occurring autoantibodies to these aggregates are proposed to be potential early-stage biomarkers to facilitate the diagnosis of PD. However, upon misfolding, alpha S forms a multitude of quaternary structures of varying functions that are unstable ex vivo. Thus, when used as a capture agent in enzyme-linked immunosorbent assays (ELISAs), significant variance among laboratories has prevented the development of these valuable diagnostic tests. We reasoned that those conflicting results arise due to the high nonspecific binding and amyloid nucleation that are typical of ELISA platforms. In this work, we describe a multiplexed, easy-to-operate immunoassay that is generally applicable to quantify the levels of amyloid proteins and their binding partners, named Oxaziridine-Assisted Solid-phase Immunosorbent (OASIS) assay. The assay is built on a hydrophilic poly(ethylene glycol) scaffold that inhibits aggregate nucleation, which we show reduces assay variance when compared to similar ELISA measurements. To validate our OASIS assay in patient-derived samples, we measured the levels of naturally occurring antibodies against the alpha S monomer and oligomers in a cohort of donor plasma from patients diagnosed with PD. Using OASIS assays, we observed significantly higher titers of immunoglobulin G antibody recognizing alpha S oligomers in PD patients compared to those in healthy controls, while there was no significant difference in naturally occurring antibodies against the alpha S monomer. In addition to its development into a blood test to potentially predict or monitor PD, we anticipate that the OASIS assay will be of high utility for studies aimed at understanding protein misfolding, its pathology and symptomology in PD, and other neurodegenerative diseases.
类型	Article
语种	英语
收录类别	SCI-E
WOS记录号	WOS:000743686200001
WOS关键词	PARKINSONS-DISEASE ; ALZHEIMERS-DISEASE ; A-BETA ; STRUCTURAL-CHARACTERIZATION ; AGGREGATION ; OLIGOMERS ; ASSAY ; BINDING ; BIOMARKERS ; DISCOVERY
WOS类目	Biochemical Research Methods ; Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary ; Chemistry, Organic
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/376569
推荐引用方式 GB/T 7714	Ge, Peng,Yang, Mu,Bouchard, Jacob L.,et al. Chemoselective Bioconjugation of Amyloidogenic Protein Antigens to PEGylated Microspheres Enables Detection of alpha-Synuclein Autoantibodies in Human Plasma[J],2022,33(2):301-310.
APA	Ge, Peng.,Yang, Mu.,Bouchard, Jacob L..,Dzamko, Nicolas.,Lewis, Simon J. G..,...&Doran, Todd M..(2022).Chemoselective Bioconjugation of Amyloidogenic Protein Antigens to PEGylated Microspheres Enables Detection of alpha-Synuclein Autoantibodies in Human Plasma.BIOCONJUGATE CHEMISTRY,33(2),301-310.
MLA	Ge, Peng,et al."Chemoselective Bioconjugation of Amyloidogenic Protein Antigens to PEGylated Microspheres Enables Detection of alpha-Synuclein Autoantibodies in Human Plasma".BIOCONJUGATE CHEMISTRY 33.2(2022):301-310.