Blood biomarker for Parkinson disease: peptoids

Yazdani, Umar; Zaman, Sayed; Hynan, Linda S.; Brown, Lamar; Dewey, Richard B.; Karp, David R.; German, Dwight C.

doi:10.1038/npjparkd.2016.12

Cited by 18 publications

(20 citation statements)

References 37 publications

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“…11 The PD patients had the disease for several years and were taking medications for treatment of the symptoms. This same antibody biomarker was 84% accurate for the identification of de novo PD patients.…”

Section: Discussionmentioning

confidence: 99%

“…11 In brief, synthesis is performed by stepwise addition of acylated amines to the solid support (Rink amide resin) starting from the carboxy terminus to the amino terminus (see Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

“…11 Plates were incubated in TMB substrate for 16 min at room temp and stopped with 2 mol/L H 2 SO 4 . Plates were read at 450 nm (CLARIOstar, BMG Labtech, USA).…”

Section: Methodsmentioning

confidence: 99%

“… 8 – 10 Previous work in our laboratory found a promising antibody biomarker, which we called PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects and was 68% accurate in identifying PD. 11 The PD2 peptoid was 84% accurate in identifying de novo PD. This result prompted us to further investigate and validate the accuracy of the PD2 biomarker for the identification of de novo PD.…”

Section: Introductionmentioning

confidence: 95%

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Antibody biomarker for de novo Parkinson disease: attempted validation

Feng

Simanski

Islam

et al. 2018

npj Parkinson's Disease

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Parkinson disease (PD) is a progressive neurodegenerative disease with motor symptoms that result from degeneration of midbrain dopaminergic neurons. Biomarker research seeks to identify the disease during the pre-symptomatic phase, which is a time when therapeutic intervention will be most helpful. Previously, we screened a combinatorial peptoid library to search for antibodies that are present at much higher levels in the serum of PD patients than in control subjects. One such compound, called the PD2 peptoid, was 84% accurate for the identification of de novo PD when employed as the capture agent in an enzyme-linked immunosorbent assay. This peptoid recognized an IgG3 antibody, and IgG3 levels were also found to be significantly higher in PD vs. control serum. In that study we used samples from the NINDS Parkinson’s Disease Biomarker Program. The current study sought to validate that finding using serum samples from de novo and control subjects in the Parkinson’s Progression Markers Initiative study. We found no difference in levels of antibodies captured by the PD2 peptoid in the de novo PD vs. control subjects, and no difference in IgG3 serum levels in the two groups. The failure to replicate our previous study appears to be due to the lack of difference in serum IgG3 levels between the PD and control subjects in the current study.

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Section: Discussionmentioning

confidence: 99%

“…11 In brief, synthesis is performed by stepwise addition of acylated amines to the solid support (Rink amide resin) starting from the carboxy terminus to the amino terminus (see Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

“…11 Plates were incubated in TMB substrate for 16 min at room temp and stopped with 2 mol/L H 2 SO 4 . Plates were read at 450 nm (CLARIOstar, BMG Labtech, USA).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Antibody biomarker for de novo Parkinson disease: attempted validation

Feng

Simanski

Islam

et al. 2018

npj Parkinson's Disease

Self Cite

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“…This approach has been used to discover a peptoid ligand with nanomolar binding affinity that is selective for Aβ 56,57 . In this manner, potential IgG antibody biomarkers have been discovered within an animal model of multiple sclerosis and human subjects with AD 58 and PD 59 . Peptoids may also be leveraged for imaging applications to add specificity to contrast and imaging agents.…”

Section: Peptoids For Biomarker Detection and Imagingmentioning

confidence: 99%

Peptoids: Emerging Therapeutics for Neurodegeneration

Moss¹

2017

J Neurol Neuromedicine

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In recent decades, the increasing prevalence of age-associated neurodegenerative diseases has underscored the need for targeted therapeutic strategies and novel diagnostics. Peptide-based neurotherapeutics offer high specificity and tolerability but are limited by proteolytic degradation in vivo. Peptoids, or N-substituted glycines, are versatile peptidomimetics that evade proteolytic degradation yet maintain many qualities that render peptides attractive neurotherapeutic candidates. These molecules may be engineered to their application through modifications that enhance structural stability and reactivity and can withstand various physiological stressors to retain their intended function within anomalous microenvironments.Peptoids generally demonstrate greater cellular permeability than their corresponding peptides, are less immunogenic, and can be administered intranasally, all properties that enhance their potential as neurotherapeutics. Peptoids have primarily been explored as aggregation inhibitors to prevent the deleterious protein plaque deposition associated with several neurodegenerative disorders. However, novel research has uncovered the potential of peptoids toward additional neurotherapeutic applications. Peptoids can modulate cell signaling pathways involved in axonal function and current modulation and can block cell signaling events associated with apoptosis. In addition, these peptidomimetics are able to function as anti-inflammatory agents via multiple mechanisms. Moreover, the versatility and low cost of peptoids render them ideal instruments in biomarker detection, discovery, and imaging. This mini-review explores these diverse applications of peptoids within the context of neurodegenerative disease.

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