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.