The predictive value of SS-16 in clinically diagnosed Parkinson’s disease patients:comparison with ^(99m)Tc-TRODAT-1 SPECT scans

Background:Dopamine transporter based imaging has high diagnostic performance in distinguishing patients with Parkinson’s disease(PD)from patients with non-Parkinsonian syndromes.Our previous study indicated that the“Sniffin’Sticks”odor identification test(SS-16)acts as a valid instrument for olfactory assessment in Chinese PD patients.The aim of the study was to compare the efficacy of the two methods in diagnosing PD.Methods:Fifty-two PD patients were involved in this study and underwent single photon emission computed tomography(SPECT)imaging using the labeled dopamine transporter radiotracer ^(99)mTc-TRODAT-1 to assess nigrostriatal dopaminergic function.Olfactory function was assessed with the“Sniffin’Sticks”odor identification test(SS-16)in all patients who received DAT-SPECT scanning.Statistical analysis(SPSS version 21)was carried out to determine the diagnostic accuracy of SS-16 as well as its correlation with ^(99)mTc-TRODAT-1 SPECT,its positive predictive value(PPV),and negative predictive value(NPV).Results:We identified a negative correlation between SS-16 and DAT SPECT(Kappa=0.269,p=0.004).By using the ^(99)mTc-TRODAT-1 uptake results as the gold standard,the sensitivity and specificity of SS-16 was 56.8 and 37.5%,respectively.Furthermore,the negative and positive predictive values were calculated as 13.6 and 83.3%,respectively.Conclusions:SS-16 would not be used as a diagnostic tool for early stage PD patients.Negative results of SS-16 would not exclude the diagnosis of PD.Further tests are needed for validation.

Neurodegenerative diseases:a hotbed for splicing defects and the potential therapies

Precursor messenger RNA(pre-mRNA)splicing is a fundamental step in eukaryotic gene expression that systematically removes non-coding regions(introns)and ligates coding regions(exons)into a continuous message(mature mRNA).This process is highly regulated and can be highly flexible through a process known as alternative splicing,which allows for several transcripts to arise from a single gene,thereby greatly increasing genetic plasticity and the diversity of proteome.Alternative splicing is particularly prevalent in neuronal cells,where the splicing patterns are continuously changing to maintain cellular homeostasis and promote neurogenesis,migration and synaptic function.The continuous changes in splicing patterns and a high demand on many cis-and trans-splicing factors contribute to the susceptibility of neuronal tissues to splicing defects.The resultant neurodegenerative diseases are a large group of disorders defined by a gradual loss of neurons and a progressive impairment in neuronal function.Several of the most common neurodegenerative diseases involve some form of splicing defect(s),such as Alzheimer’s disease,Parkinson’s disease and spinal muscular atrophy.Our growing understanding of RNA splicing has led to the explosion of research in the field of splice-switching antisense oligonucleotide therapeutics.Here we review our current understanding of the effects alternative splicing has on neuronal differentiation,neuronal migration,synaptic maturation and regulation,as well as the impact on neurodegenerative diseases.We will also review the current landscape of splice-switching antisense oligonucleotides as a therapeutic strategy for a number of common neurodegenerative disorders.

Methylation status of DJ-1 in leukocyte DNA of Parkinson’s disease patients

Background:DJ-1 has been thought as a candidate biomarker for Parkinson’s disease(PD).It was found reduced in PD brains,CSF and saliva,although there were conflicting results.How DJ-1 expression may be regulated is not clear.Recently,blood-based DNA methylation represents a highly promising biomarker for PD by regulating the causative gene expression.Thus,in this study,we try to explore whether blood-based DNA methylation of DJ-1 could be used as a biomarker to differentiate PD patients from normal control(NC),and whether DNA methylation could regulate DJ-1 expression in a SH-SY5Y cell model.Methods:Forty PD patients and 40 NC were recruited in this study.DNA was extracted from peripheral blood leukocytes(PBLs).Methylation status of two CpG islands(CpG1 and CpG2)in promoter region of DJ-1 was explored by bisulfite specific PCR-based sequencing method.Methylation inhibitor 5-Aza-dC was used to treat SH-SY5Y cell line,DJ-1 level was detected in both mRNA and protein level.Results:CpG sites in these two CpG islands(CpG1 and CpG2)of DJ-1 were unmethylated in both PD and NC group.In SH-SY5Y cell model treated by methylation inhibitor,there was no significant change of DJ-1 expression in either mRNA level or protein level.Conclusions:Our results indicated that DNA methylation inhibitor didn’t alter DJ-1 gene expression in SH-SY5Y cell model,and DNA methylation of DJ-1 promoter region in PBLs level might not be an efficient biomarker for PD patients.