Cross-Reactive Antibodies to Target Proteins are Dependent upon Oligomannose Glycosylated Epitopes in HTLV-1 Associated Neurological Disease

Lee, Sang‐Min; Shin, Yoojin; Clark, Daniel; Gotuzzo, Eduardo; Levin, Michael C.

doi:10.1007/s10875-012-9652-9

Cited by 3 publications

(3 citation statements)

References 53 publications

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“…For example, a recent study showed that autoantibodies to the potassium channel KIR4.1, a glial protein, might contribute to the pathogenesis of MS. 124,125 A potential role for antibodies to the RBP hnRNP A1 in the pathogenesis of neurodegeneration in MS and HAM/TSP Data generated in our lab also indicate that antibodies to the nonmyelin compartment, specifically neurons, may contribute to the pathogenesis of MS and HAM/TSP. [11][12][13][14][126][127][128][129] Initially, submit your manuscript | www.dovepress.com Dovepress Dovepress using neuronal proteins purified from human brain, IgG isolated from HAM/TSP patients was found to immunoreact with a 33 kDa protein by Western blot. 126 Subsequently, the protein was identified as heterogeneous nuclear ribonuclear protein A1 (hnRNP A1).…”

Section: Antibodies As Contributors To Neurodegeneration and The Pathmentioning

confidence: 99%

Pathogenic mechanisms of neurodegeneration based on the phenotypic expression of progressive forms of immune-mediated neurologic disease

Levin¹,

Lee²,

Gardner³

et al. 2012

DNND

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Considering there are no treatments for progressive forms of multiple sclerosis (MS), a comprehensive understanding of the role of neurodegeneration in the pathogenesis of MS should lead to novel therapeutic strategies to treat it. Many studies have implicated viral triggers as a cause of MS, yet no single virus has been exclusively shown to cause MS. Given this, human and animal viral models of MS are used to study its pathogenesis. One example is human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Importantly, HAM/TSP is similar clinically, pathologically, and immunologically to progressive MS. Interestingly, both MS and HAM/TSP patients were found to make antibodies to heterogeneous nuclear ribonucleoprotein (hnRNP) A1, an RNA-binding protein overexpressed in neurons. Anti-hnRNP A1 antibodies reduced neuronal firing and caused neurodegeneration in neuronal cell lines, suggesting the autoantibodies are pathogenic. Further, microarray analyses of neurons exposed to anti-hnRNP A1 antibodies revealed novel pathways of neurodegeneration related to alterations of RNA levels of the spinal paraplegia genes (SPGs). Mutations in SPGs cause hereditary spastic paraparesis, genetic disorders clinically indistinguishable from progressive MS and HAM/TSP. Thus, there is a strong association between involvement of SPGs in neurodegeneration and the clinical phenotype of progressive MS and HAM/TSP patients, who commonly develop spastic paraparesis. Taken together, these data begin to clarify mechanisms of neurodegeneration related to the clinical presentation of patients with chronic immune-mediated neurological disease of the central nervous system, which will give insights into the design of novel therapies to treat these neurological diseases.

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Section: Antibodies As Contributors To Neurodegeneration and The Pathmentioning

confidence: 99%

Pathogenic mechanisms of neurodegeneration based on the phenotypic expression of progressive forms of immune-mediated neurologic disease

Levin¹,

Lee²,

Gardner³

et al. 2012

DNND

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“…Previously described as a predominantly demyelinating disease, MS is now considered both a disease of inflammatory-mediated demyelination and neurodegeneration (loss or damage to neurons and axons) (Peterson and Fujinami, 2007). These pathologic features are also present in HAM/TSP, which resembles progressive forms of MS clinically, but unlike MS, has been shown to be caused by infection with HTLV-1 (Jernigan et al, 2003;Lee et al, , 2012.…”

Section: Spinal Muscular Atrophy (Sma)mentioning

confidence: 99%

A Comprehensive Analysis of the Role of hnRNP A1 Function and Dysfunction in the Pathogenesis of Neurodegenerative Disease

Clarke

Thibault

Salapa

et al. 2021

Front. Mol. Biosci.

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Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a member of the hnRNP family of conserved proteins that is involved in RNA transcription, pre-mRNA splicing, mRNA transport, protein translation, microRNA processing, telomere maintenance and the regulation of transcription factor activity. HnRNP A1 is ubiquitously, yet differentially, expressed in many cell types, and due to post-translational modifications, can vary in its molecular function. While a plethora of knowledge is known about the function and dysfunction of hnRNP A1 in diseases other than neurodegenerative disease (e.g., cancer), numerous studies in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, multiple sclerosis, spinal muscular atrophy, Alzheimer’s disease, and Huntington’s disease have found that the dysregulation of hnRNP A1 may contribute to disease pathogenesis. How hnRNP A1 mechanistically contributes to these diseases, and whether mutations and/or altered post-translational modifications contribute to pathogenesis, however, is currently under investigation. The aim of this comprehensive review is to first describe the background of hnRNP A1, including its structure, biological functions in RNA metabolism and the post-translational modifications known to modify its function. With this knowledge, the review then describes the influence of hnRNP A1 in neurodegenerative disease, and how its dysfunction may contribute the pathogenesis.

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“…Decreased levels of Prdx2 were seen in the cerebral spinal fluid of such AIDS patients [ 158 ]. Moreover, the presence of cross-reactive antibodies to p24-(gag) protein of another lentivirus, human T-lymphotropic virus type-1 (HTLV-1), and peroxiredoxin 1 was noted [ 159 ]. It can be speculated that scavenging of this antioxidant enzyme can also contribute to the development of virus-associated neurological disorders.…”

Section: Peroxiredoxins and Viral Infectionsmentioning

confidence: 99%

Peroxiredoxins—The Underrated Actors during Virus-Induced Oxidative Stress

et al. 2021

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Enhanced production of reactive oxygen species (ROS) triggered by various stimuli, including viral infections, has attributed much attention in the past years. It has been shown that different viruses that cause acute or chronic diseases induce oxidative stress in infected cells and dysregulate antioxidant its antioxidant capacity. However, most studies focused on catalase and superoxide dismutases, whereas a family of peroxiredoxins (Prdx), the most effective peroxide scavengers, were given little or no attention. In the current review, we demonstrate that peroxiredoxins scavenge hydrogen and organic peroxides at their physiological concentrations at various cell compartments, unlike many other antioxidant enzymes, and discuss their recycling. We also provide data on the regulation of their expression by various transcription factors, as they can be compared with the imprint of viruses on transcriptional machinery. Next, we discuss the involvement of peroxiredoxins in transferring signals from ROS on specific proteins by promoting the oxidation of target cysteine groups, as well as briefly demonstrate evidence of nonenzymatic, chaperone, functions of Prdx. Finally, we give an account of the current state of research of peroxiredoxins for various viruses. These data clearly show that Prdx have not been given proper attention despite all the achievements in general redox biology.

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Cross-Reactive Antibodies to Target Proteins are Dependent upon Oligomannose Glycosylated Epitopes in HTLV-1 Associated Neurological Disease

Cited by 3 publications

References 53 publications

Pathogenic mechanisms of neurodegeneration based on the phenotypic expression of progressive forms of immune-mediated neurologic disease

Pathogenic mechanisms of neurodegeneration based on the phenotypic expression of progressive forms of immune-mediated neurologic disease

A Comprehensive Analysis of the Role of hnRNP A1 Function and Dysfunction in the Pathogenesis of Neurodegenerative Disease

Peroxiredoxins—The Underrated Actors during Virus-Induced Oxidative Stress

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