Identification and quantification of differentially expressed proteins in plasma of spinocerebellar ataxia type 12

Swarup, Vishnu; Srivastava, Achal K.; Rajeswari, Moganty R.

doi:10.1016/j.neures.2012.03.002

Cited by 8 publications

(10 citation statements)

References 28 publications

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“…3A,B). Earlier reports on dysregulated lipid metabolism in a number of neurodegenerative diseases, including Alzheimer's, Parkinson's, Niemann-Pick's, and Huntington's diseases (Adibhatla and Hatcher, 2008); spinocerebellar ataxia type 12 (Swarup et al, 2012); and spinocerebellar ataxia type 2 (Swarup et al, 2013), support the present observations found in FRDA. Low levels of apoC-II and C-III obtained in plasma of FRDA patients in our study indicate their possible role in altered lipid metabolism among FRDA patients.…”

Section: Downregulated Proteinssupporting

confidence: 91%

Quantitative profiling and identification of differentially expressed plasma proteins in friedreich's ataxia

Swarup

Srivastava

Padma

et al. 2013

J of Neuroscience Research

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Friedreich's ataxia (FRDA) is an autosomal recessive ataxia, characterized by progressive gait ataxia, limb ataxia, dysarthria, and areflexia associated with diabetes and hypertrophic cardiomyopathy. The primary cause of FRDA is the presence of expanded DNA triplet (GAA) repeats in the first intron of the fxn gene on chromosome 9q13. The expanded DNA repeats in fxn inhibit expression of the protein frataxin, which leads to neuronal degeneration. The aim of the study was to identify differentially expressed plasma proteins in FRDA patients for their diagnostic/prognostic applications. Clinically suspected FRDA patients (n = 42) were assessed on the International Co-Operative Ataxia Rating Scale (ICARS), and genetic confirmation was performed by analyzing (GAA) repeats via PCR. Eighteen patients were confirmed to be homozygous for FRDA, with ICARS scores of 40 ± 8. Plasma proteomics of homozygous FRDA patients and age- and gender-matched healthy controls was done using two-dimensional difference in-gel electrophoresis and LC-MS/MS. Quantitative proteomic analysis (fold change ≥1.5; P < 0.05) revealed 13 differentially expressed protein spots. These proteins were found to be associated with neuropathy (α1-antitrypsin), ataxia (apolipoprotein A-I), oxidative stress (albumin), altered lipid metabolism (apolipoprotein C-II, C-III), etc. Further investigations of these differentially expressed proteins can aid in identifying prognostic/diagnostic markers for FRDA.

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Section: Downregulated Proteinssupporting

confidence: 91%

Quantitative profiling and identification of differentially expressed plasma proteins in friedreich's ataxia

Swarup

Srivastava

Padma

et al. 2013

J of Neuroscience Research

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“…table s1). Recent reports from our group on SCA type 12 (from mostly northern India) [17] and a report on SCA type 2 and 3 patients representing southern India [28] clearly reveal a strong neuropathy in SCA patients. An interesting case report by Ng et al [29] on a patient who had complete deficiency of apolipoprotein A-1 co-presented with ataxia, neuropathy, multifocal central nervous system deficits and electrophysiologic abnormalities suggested a direct correlation between apoA-I levels and pathological conditions.…”

Section: Discussionmentioning

confidence: 65%

“…Depleted protein samples were labeled using fluorescent cyanine dyes (GE Healthcare, Singapore) following the manufacturer's recommended protocols and as per our previous study [17]. The internal standard was prepared by combining equal concentrations of each of the 6 patient and 6 healthy control samples and labeled with Cy2.…”

Section: Methodsmentioning

confidence: 99%

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Quantitative Profiling and Identification of Plasma Proteins of Spinocerebellar Ataxia Type 2 Patients

Swarup

Srivastava²,

Padma³

et al. 2013

Neurodegener Dis

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Background: Spinocerebellar ataxia type 2 (SCA2) is an autosomal-dominant hereditary ataxia characterized by progressive gait and limb ataxia, dysarthria, slow saccades, neuropathy and dementia. The expansion of trinucleotide CAG repeats in the coding region of the ATXN-2 gene leads to expanded polyglutamine stretch in the mutated protein which causes neuronal death. Objective: In this study, we investigated the blood plasma of SCA2 patients to find protein biomarkers. Methods: Thirty-two ataxia patients clinically suspected for SCA2 were evaluated by the International Co-operative Ataxia Rating Scale followed by genetic analysis using PCR. Plasma proteomics of SCA2 patients and age- and gender-matched healthy controls was done using 2D-difference in-gel electrophoresis, LC-MS/MS and Western blot. Results: Genetic analysis confirmed 10 of 32 suspected SCA2 patients. Proteomic data revealed nine differentially expressed proteins in SCA2. These proteins find good association with oxidative stress, calcium-dependent apoptosis, neuropathy, and cognitive impairment in SCA2 patients. Interestingly, the elevated levels of the voltage-dependent calcium channel γ-3 subunit showed a direct correlation with calcium-generated apoptosis of Purkinje cells. The cognitive deficit, a common symptom in SCA2 patients, seems to correlate with decreased levels of transthyretin and retinol-binding protein-4. Conclusions: Some of these identified proteins in SCA2 can be useful for therapeutic, diagnostic and prognostic purposes.

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“…APOC2 is a cofactor for the activation of lipoprotein lipase that mediates hydrolysis of triglycerides, and plays an important role in the transport of lipids in the CNS [ 57 , 58 ]. Apolipoprotein C2 deficiency is related to a lipid encephalopathy and spinocerebellar ataxia type 12 [ 59 , 60 ]. In contrast to the other three orthologues, APOC2 level in the CSF showed a strong positive correlation with the concentration of proinflammatory IL-2, IL-16, and CCL26/eotaxin-3.…”

Section: Discussionmentioning

confidence: 99%

Orthologous proteins of experimental de- and remyelination are differentially regulated in the CSF proteome of multiple sclerosis subtypes

et al. 2018

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ObjectiveHere, we applied a multi-omics approach (i) to examine molecular pathways related to de- and remyelination in multiple sclerosis (MS) lesions; and (ii) to translate these findings to the CSF proteome in order to identify molecules that are differentially expressed among MS subtypes.MethodsTo relate differentially expressed genes in MS lesions to de- and remyelination, we compared transcriptome of MS lesions to transcriptome of cuprizone (CPZ)-induced de- and remyelination. Protein products of the overlapping orthologous genes were measured within the CSF by quantitative proteomics, parallel reaction monitoring (PRM). Differentially regulated proteins were correlated with molecular markers of inflammation by using MesoScale multiplex immunoassay. Expression kinetics of differentially regulated orthologous genes and proteins were examined in the CPZ model.ResultsIn the demyelinated and remyelinated corpus callosum, we detected 1239 differentially expressed genes; 91 orthologues were also differentially expressed in MS lesions. Pathway analysis of these orthologues suggested that the TYROBP (DAP12)-TREM2 pathway, TNF-receptor 1, CYBA and the proteasome subunit PSMB9 were related to de- and remyelination. We designed 129 peptides representing 51 orthologous proteins, measured them by PRM in 97 individual CSF, and compared their levels between relapsing (n = 40) and progressive MS (n = 57). Four proteins were differentially regulated among relapsing and progressive MS: tyrosine protein kinase receptor UFO (UFO), TIMP-1, apolipoprotein C-II (APOC2), and beta-2-microglobulin (B2M). The orthologous genes/proteins in the mouse brain peaked during acute remyelination. UFO, TIMP-1 and B2M levels correlated inversely with inflammation in the CSF (IL-6, MCP-1/CCL2, TARC/CCL17). APOC2 showed positive correlation with IL-2, IL-16 and eotaxin-3/CCL26.ConclusionsPathology-based multi-omics identified four CSF markers that were differentially expressed in MS subtypes. Upregulated TIMP-1, UFO and B2M orthologues in relapsing MS were associated with reduced inflammation and reflected reparatory processes, in contrast to the upregulated orthologue APOC2 in progressive MS that reflected changes in lipid metabolism associated with increased inflammation.

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Identification and quantification of differentially expressed proteins in plasma of spinocerebellar ataxia type 12

Cited by 8 publications

References 28 publications

Quantitative profiling and identification of differentially expressed plasma proteins in friedreich's ataxia

Quantitative profiling and identification of differentially expressed plasma proteins in friedreich's ataxia

Quantitative Profiling and Identification of Plasma Proteins of Spinocerebellar Ataxia Type 2 Patients

Orthologous proteins of experimental de- and remyelination are differentially regulated in the CSF proteome of multiple sclerosis subtypes

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