title: Quantitative profiling and identification of plasma proteins of spinocerebellar ataxia type 2 patients.
abstract: 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.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Vishnu
authors.initials: V
authors.lastname: Swarup
authors.forename: Achal K
authors.initials: AK
authors.lastname: Srivastava
authors.forename: Madakasira V
authors.initials: MV
authors.lastname: Padma
authors.forename: Rajeswari R
authors.initials: RR
authors.lastname: Moganty
mesh_terms: D000293:Adolescent; D000328:Adult; D000067528:Ataxins; D001798:Blood Proteins / Q000378:metabolism*; D002853:Chromatography, Liquid; D019295:Computational Biology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D010455:Peptides / Q000235:genetics; D012189:Retrospective Studies; D020754:Spinocerebellar Ataxias / Q000097:blood* / Q000235:genetics; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D000067528:Ataxins; D001798:Blood Proteins; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D010455:Peptides; C097188:polyglutamine