Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect...Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.展开更多
目的应用心率变异性(heart rate variability,HRV)及皮肤交感神经活性(skin sympathetic nerve activity,SKNA)的方法,探讨持续非卧床腹膜透析(continuous ambulatory peritoneal dialysis,CAPD)与维持性血液透析(maintenance hemodialy...目的应用心率变异性(heart rate variability,HRV)及皮肤交感神经活性(skin sympathetic nerve activity,SKNA)的方法,探讨持续非卧床腹膜透析(continuous ambulatory peritoneal dialysis,CAPD)与维持性血液透析(maintenance hemodialysis,MHD)患者在单次透析过程中自主神经张力变化及差异。方法纳入2021年2月─7月在南京医科大学第一附属医院肾科住院的CAPD患者及血液透析中心MHD患者,自透析开始(MHD患者自48h间隔后上机,CAPD患者晨起时更换夜间留腹透析液)采集4 h连续高频心电信号,依据透析方式不同分为CAPD组及MHD组,并比较2组患者透析中每30 min平均心率、全部正常窦性心搏间期的标准差(standard deviation of the interbeat interval of normal sinus beats,SDNN)、标准化低频功率(normalized low frequency power,LFn)、标准化高频功率(normalized high frequency power,HFn)、低频高频功率比值(LF/HF)及SKNA平均电压(average voltage of SKNA,aSKNA)的变化及组间差异。结果共纳入30例CAPD及50例MHD患者。2组患者第1、2个30 min的平均心率(t=-2.210、-2.426,P=0.037,0.018)及HFn(Z=2.226、2.027,P=0.026、0.043)有统计学差异,第2个30 min的LFn有统计学差异(t=-2.548,P=0.013)。透析后,2组患者均表现出LF/HF升高(Z=3.162,2.980,P=0.011,0.020),MHD组变化更早;MHD组平均心率增加(q=3.336,P=0.009),HFn降低(Z=4.123,P<0.001)。各时段aSKNA 2组相比无统计学差异(0.010<|Z|<1.109,均P>0.05),但MHD组动态变化更大(Z>3.125,P<0.05)。结论MHD患者较CAPD患者在单次透析中自主神经指标变化更大。展开更多
基金supported by the Science and Technology(S&T)Program of Hebei Province,No.22377798D(to YZ).
文摘Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.
文摘目的应用心率变异性(heart rate variability,HRV)及皮肤交感神经活性(skin sympathetic nerve activity,SKNA)的方法,探讨持续非卧床腹膜透析(continuous ambulatory peritoneal dialysis,CAPD)与维持性血液透析(maintenance hemodialysis,MHD)患者在单次透析过程中自主神经张力变化及差异。方法纳入2021年2月─7月在南京医科大学第一附属医院肾科住院的CAPD患者及血液透析中心MHD患者,自透析开始(MHD患者自48h间隔后上机,CAPD患者晨起时更换夜间留腹透析液)采集4 h连续高频心电信号,依据透析方式不同分为CAPD组及MHD组,并比较2组患者透析中每30 min平均心率、全部正常窦性心搏间期的标准差(standard deviation of the interbeat interval of normal sinus beats,SDNN)、标准化低频功率(normalized low frequency power,LFn)、标准化高频功率(normalized high frequency power,HFn)、低频高频功率比值(LF/HF)及SKNA平均电压(average voltage of SKNA,aSKNA)的变化及组间差异。结果共纳入30例CAPD及50例MHD患者。2组患者第1、2个30 min的平均心率(t=-2.210、-2.426,P=0.037,0.018)及HFn(Z=2.226、2.027,P=0.026、0.043)有统计学差异,第2个30 min的LFn有统计学差异(t=-2.548,P=0.013)。透析后,2组患者均表现出LF/HF升高(Z=3.162,2.980,P=0.011,0.020),MHD组变化更早;MHD组平均心率增加(q=3.336,P=0.009),HFn降低(Z=4.123,P<0.001)。各时段aSKNA 2组相比无统计学差异(0.010<|Z|<1.109,均P>0.05),但MHD组动态变化更大(Z>3.125,P<0.05)。结论MHD患者较CAPD患者在单次透析中自主神经指标变化更大。
