Antibodies to Potato Virus Y Bind the Amyloid β Peptide

Friedland, Robert P.; Tedesco, Johnathan M.; Wilson, Allen D.; Atwood, Craig S.; Smith, Mark A.; Perry, George; Zagorski, Michael G.

doi:10.1074/jbc.m802088200

Cited by 26 publications

(28 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…PVY is found worldwide, and it is estimated that 15% of potato crops are infected. It is likely that some potatoes consumed by humans are infected with PVY 34 . Previous studies have shown similarities between this plant virus protein and amyloid Aβ 1–42 peptide, a protein found in plaques in Alzheimer-diseased brains.…”

Section: Resultsmentioning

confidence: 90%

“…Previous studies have shown similarities between this plant virus protein and amyloid Aβ 1–42 peptide, a protein found in plaques in Alzheimer-diseased brains. Specifically, mouse antibodies to PVY bind to amyloid Aβ 34 . An analysis showed sequence similarity of PVY with five human miRs including hsa-mir-1243, hsa-mir-101-1, hsa-mir-105-1, hsa-mir-105-2 and hsa-mir-1182 (Table 4).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Cross-kingdom sequence similarities between human micro-RNAs and plant viruses

Rebolledo-Mendez¹,

Vaishnav

Cooper³

et al. 2013

Communicative & Integrative Biology

View full text Add to dashboard Cite

Micro-RNAs regulate the expression of cellular and tissue phenotypes at a post-transcriptional level through a complex process involving complementary interactions between micro-RNAs and messenger-RNAs. Similar nucleotide interactions have been shown to occur as cross-kingdom events; for example, between plant viruses and plant micro-RNAs and also between animal viruses and animal micro-RNAs. In this study, this view is expanded to look for cross-kingdom similarities between plant virus and human micro-RNA sequences. A method to identify significant nucleotoide sequence similarities between plant viruses and hsa micro-RNAs was created. Initial analyses demonstrate that plant viruses contain nucleotide sequences which exactly match the seed sequences of human micro-RNAs in both parallel and anti-parallel directions. For example, the bean common mosaic virus strain NL4 from Colombia contains sequences that match exactly the seed sequence for micro-RNA of the hsa-mir-1226 in the parallel direction, which suggests a cross-kingdom conservation. Similarly, the rice yellow stunt viral cRNA contains a sequence that is an exact match in the anti-parallel direction to the seed sequence of hsa-micro-RNA let-7b. The functional implications of these results need to be explored. The finding of these cross-kingdom sequence similarities is a useful starting point in support of bench level investigations.

show abstract

Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Cross-kingdom sequence similarities between human micro-RNAs and plant viruses

Rebolledo-Mendez¹,

Vaishnav

Cooper³

et al. 2013

Communicative & Integrative Biology

View full text Add to dashboard Cite

show abstract

“…In fact, our findings do not support studies describing a general increase in autoantibody titers to endogenous antigens with age in humans (54), but may be more consistent with an age-related decrease of immune response to exogenous antigens (54) that mimic amyloidogenic peptides. In support of this, new evidence in mice indicates that at least some A␤ antibodies may be induced by a peptide sequence in the common potato virus Y (PVY) homologous to the N terminus of A␤ (55). Antibodies against PVY were also isolated in a screen of a human synthetic phage-antibody library (56), but it remains unknown whether the general population develops a specific immune response to PVY with cross-reactivity to A␤.…”

Section: Discussionmentioning

confidence: 92%

Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease

Britschgi¹,

Olin²,

Johns³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

168

163

View full text Add to dashboard Cite

A number of distinct ␤-amyloid (A␤) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural A␤-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic A␤ and amyloidogenic non-A␤ species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21-89 years. Antibody reactivity was most prominent against oligomeric assemblies of A␤ and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of A␤1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant A␤, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from A␤ toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with A␤ the monkeys developed high titers not only against A␤ peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of A␤ antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD. A lzheimer's disease (AD) is the most common cause of dementia, affecting an estimated 5.3 million individuals in the United States alone. Deposits of ␤-amyloid peptide (A␤) in extracellular plaques characterize the AD brain, but soluble oligomeric A␤ species appear to be more neurotoxic than plaques and interfere with synaptic function (reviewed in ref. 1). Notably, most A␤ peptides isolated from AD brains are posttranslationally modified and truncated (2-6), and some are proposed to be oxidized (7,8) or cross-linked at Tyr-10 (9). Although the pathogenic consequences of these modifications need to be resolved, most of them can stabilize A␤ assemblies, interfere with proteolytic degradation, and increase A␤ toxicity in vitro (7,8,10).One line of defense against toxic A␤ species could be neutralizing antibodies. Stimulating the production of A␤ antibodies by active immunization with synthetic A␤ (11) or administering monoclonal A␤ antibodies (12, 13) reduced amyloid pathology and inflammation and improved cognitive function in mouse models of AD (14). In patients with mild to moderate AD active immunization appears to reduce plaque load (15), and in some patients production of A␤ antibodies correlated with attenuated cognitive decline (16). It has also been suggested that antibodies recognizing different domains (12,13,17) or conformations (18, 19) of A␤ may have different efficacy in humans.Interestingly, antibodies agai...

show abstract

“…However, mice injected with a small amount of Aβ after feeding with transgenic tomato developed high titers of anti-Aβ antibodies, suggesting that mice acquired immune conditioning by eating Aβ -containing tomato (Youm et al 2008). Similar effect may be obtained by eating potato infected with virus which has high homology with Aβ (Friedland et al 2008).…”

Section: Recombinant Vegetable Recombinant Bacteria Recombinant Phagementioning

confidence: 71%

Immunization Therapy for Alzheimer Disease: A Comprehensive Review of Active Immunization Strategies

Tabira

2010

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Antibodies to Potato Virus Y Bind the Amyloid β Peptide

Cited by 26 publications

References 58 publications

Cross-kingdom sequence similarities between human micro-RNAs and plant viruses

Cross-kingdom sequence similarities between human micro-RNAs and plant viruses

Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease

Immunization Therapy for Alzheimer Disease: A Comprehensive Review of Active Immunization Strategies

Contact Info

Product

Resources

About