Accumulation of aberrant proteins and inclusion bodies are hallmarks in most neurodegenerative diseases. Consequently, these aggregates within neurons lead to toxic effects, overproduction of reactive oxygen species a...Accumulation of aberrant proteins and inclusion bodies are hallmarks in most neurodegenerative diseases. Consequently, these aggregates within neurons lead to toxic effects, overproduction of reactive oxygen species and oxidative stress. Autophagy is a significant intracellular mechanism that removes damaged organelles and misfolded proteins in order to maintain cell homeostasis. Excessive or insufficient autophagic activity in neurons leads to altered homeostasis and influences their survival rate, causing neurodegeneration. The review article provides an update of the role of autophagic process in representative chronic and acute neurodegenerative disorders.展开更多
AIM： To investigate the role of O-GIcNAcylation of nuclear factor-kappa B （NF-KB） in retinal ganglion cell （RGC） death and analysedthe effect of Aralia elata （AE） on neurodegen- eration in diabetic mice. METH...AIM： To investigate the role of O-GIcNAcylation of nuclear factor-kappa B （NF-KB） in retinal ganglion cell （RGC） death and analysedthe effect of Aralia elata （AE） on neurodegen- eration in diabetic mice. METHODS： C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control （CTL） diet at the onset of diabetes mellitus （DM）. Two months af- tar injection of streptozotocin or saline, the degree of cell death and the expression of O-GIcNAc transferase （OGT）, N-acetyl-b-D-glucosaminidase （OGA）, O-GIcNAcylated pro- teins, and O-GIcNAcylation of NF-KB were examined. RESULTS： AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness （P〈0.001 vs CTL, P〈0.01 vs DM） and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling （P〈0.001 vs CTL, P〈0.0001 vs DM）, glial activation, and active caspase-3 （P〈0.0001 vs CTL, P〈0.0001 vs DM） were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GIcNAcylation and OGT were increased in diabetic retinas （P〈0.0001 vs CTL）, and the level of O-GIcNAcylation of the NF-KB p65 subunit was higher in diabetic retinas than in controls （P〈0.0001 vs CTL）. AE extract downregulated O-GIcNAcylation of NF-KB and prevented neurodegeneration induced by hyperglycemia （P〈0.0001 vs DM）. CONCLUSION： O-GIcNAcylation of NF-KB is concerned in neuronal degeneration and that AE prevents diabetes-in- duced RGC apoptosis via downregulation of NF-KB O-GI- cNAcylation. Hence, O-GIcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic pos- sibility to prevent diabetes-induced neurodegeneration.展开更多
Nurr1 defects could in part underlie Parkinson’s disease pathogenesis,and Nurr1 gene polymorphism has been found in Caucasian patients with Parkinson’s disease.In this study,heteroduplex technology was applied to co...Nurr1 defects could in part underlie Parkinson’s disease pathogenesis,and Nurr1 gene polymorphism has been found in Caucasian patients with Parkinson’s disease.In this study,heteroduplex technology was applied to compare the DNA sequences of eight exons of Nurr1 among 200 sporadic Parkinson’s disease patients and 200 healthy controls in the Han population in the Hubei province,China.One allele amplified from exon 3 of Nurr1 was polymorphic in five Parkinson’s disease patients（2.5%,5/200）,and two individuals had a polymorphic allele amplified from exon 2 （1%,2/200）.The anomalous electrophoresis fragment in exon 3 of Nurr1 gene contained a 709C/A missense mutation,and a polymorphic single nucleotide polymorphism at 388G/A was identified in exon 2.Compared with the control group,the Nurr1 gene expression level in the Parkinson’s disease group was decreased,and the Nurr1 gene expression levels in Parkinson’s disease patients carrying the polymorphisms at exons 2 and 3 were significantly decreased.Our data indicate that the single nucleotide polymorphism 388G/A in exon 2 and the 709C/A missense mutation in exon 3 of the Nurr1 gene in the Chinese population might affect the pathogenesis of Parkinson’s disease.展开更多
Chromosome microarray analysis(CMA) is a cost-effective molecular cytogenetic technique that has been used as a first-line diagnostic test in neurodevelopmental disorders in the USA since 2011. The impact of CMA resul...Chromosome microarray analysis(CMA) is a cost-effective molecular cytogenetic technique that has been used as a first-line diagnostic test in neurodevelopmental disorders in the USA since 2011. The impact of CMA results on clinical practice in China is not yet well studied, so we aimed to better evaluate this phenomenon.We analyzed the CMA results from 434 patients in our clinic, and characterized their molecular diagnoses, clinical features, and follow-up clinical actions based on these results. The overall diagnostic yield for our patients was 13.6%(59 out of 434). This gave a detection rate of 14.7%for developmental delay/intellectual disability(DD/ID,38/259) and 12% for autism spectrum disorders(ASDs,21/175). Thirty-three recurrent(n≥2) variants were found, distributed at six chromosomal loci involving known chromosome syndromes(such as DiGeorge, Williams Beuren, and Angelman/Prader-Willi syndromes).The spectrum of positive copy number variants in our study was comparable to that reported in Caucasian populations, but with specific characteristics. Parental origin tests indicated an effect involving a significant maternal transmission bias to sons. The majority of patients with positive results(94.9%) had benefits, allowing earlier diagnosis(36/59), prioritized full clinical management(28/59), medication changes(7/59), a changed prognosis(30/59), and prenatal genetic counseling(15/59). Our results provide information on de novo mutations in Chinese children with DD/ID and/or ASDs. Our data showed that microarray testing provides immediate clinical utility for patients. It is expected that the personalized medical care of children with developmental disabilities will lead to improved outcomes in long-term developmental potential.We advocate using the diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility.展开更多
文摘Accumulation of aberrant proteins and inclusion bodies are hallmarks in most neurodegenerative diseases. Consequently, these aggregates within neurons lead to toxic effects, overproduction of reactive oxygen species and oxidative stress. Autophagy is a significant intracellular mechanism that removes damaged organelles and misfolded proteins in order to maintain cell homeostasis. Excessive or insufficient autophagic activity in neurons leads to altered homeostasis and influences their survival rate, causing neurodegeneration. The review article provides an update of the role of autophagic process in representative chronic and acute neurodegenerative disorders.
基金Supported by the Basic Science Research Program Through the National Research Foundation(NRF)of Korea Funded by the Ministry of Science,ICT,and Future Planning 2014049413,NRF-2015R1A5A2008833 and NRF-2015R1C1A1A02037702
文摘AIM： To investigate the role of O-GIcNAcylation of nuclear factor-kappa B （NF-KB） in retinal ganglion cell （RGC） death and analysedthe effect of Aralia elata （AE） on neurodegen- eration in diabetic mice. METHODS： C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control （CTL） diet at the onset of diabetes mellitus （DM）. Two months af- tar injection of streptozotocin or saline, the degree of cell death and the expression of O-GIcNAc transferase （OGT）, N-acetyl-b-D-glucosaminidase （OGA）, O-GIcNAcylated pro- teins, and O-GIcNAcylation of NF-KB were examined. RESULTS： AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness （P〈0.001 vs CTL, P〈0.01 vs DM） and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling （P〈0.001 vs CTL, P〈0.0001 vs DM）, glial activation, and active caspase-3 （P〈0.0001 vs CTL, P〈0.0001 vs DM） were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GIcNAcylation and OGT were increased in diabetic retinas （P〈0.0001 vs CTL）, and the level of O-GIcNAcylation of the NF-KB p65 subunit was higher in diabetic retinas than in controls （P〈0.0001 vs CTL）. AE extract downregulated O-GIcNAcylation of NF-KB and prevented neurodegeneration induced by hyperglycemia （P〈0.0001 vs DM）. CONCLUSION： O-GIcNAcylation of NF-KB is concerned in neuronal degeneration and that AE prevents diabetes-in- duced RGC apoptosis via downregulation of NF-KB O-GI- cNAcylation. Hence, O-GIcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic pos- sibility to prevent diabetes-induced neurodegeneration.
基金supported by the Science and Technology Department of Jiangxi Province,No.20114BAB205076a Grant from the Jiangxi Provincial Health Department,No.20094008
文摘Nurr1 defects could in part underlie Parkinson’s disease pathogenesis,and Nurr1 gene polymorphism has been found in Caucasian patients with Parkinson’s disease.In this study,heteroduplex technology was applied to compare the DNA sequences of eight exons of Nurr1 among 200 sporadic Parkinson’s disease patients and 200 healthy controls in the Han population in the Hubei province,China.One allele amplified from exon 3 of Nurr1 was polymorphic in five Parkinson’s disease patients（2.5%,5/200）,and two individuals had a polymorphic allele amplified from exon 2 （1%,2/200）.The anomalous electrophoresis fragment in exon 3 of Nurr1 gene contained a 709C/A missense mutation,and a polymorphic single nucleotide polymorphism at 388G/A was identified in exon 2.Compared with the control group,the Nurr1 gene expression level in the Parkinson’s disease group was decreased,and the Nurr1 gene expression levels in Parkinson’s disease patients carrying the polymorphisms at exons 2 and 3 were significantly decreased.Our data indicate that the single nucleotide polymorphism 388G/A in exon 2 and the 709C/A missense mutation in exon 3 of the Nurr1 gene in the Chinese population might affect the pathogenesis of Parkinson’s disease.
基金supported by grants from the National Natural Science Foundation of China (81761128035 and 81781220701)the Shanghai Municipal Science and Technology Committee (17XD1403200 and 18dz2313505)+2 种基金the Research Physician Project of Shanghai Municipal Education Commission (20152234)the Shanghai Municipal Health and Family Planning Commission (GDEK201709, 2017ZZ02026, and 2017EKHWYX02)the Scientific Program of Shanghai Shenkang Hospital Development Center (16CR2025B) of China
文摘Chromosome microarray analysis(CMA) is a cost-effective molecular cytogenetic technique that has been used as a first-line diagnostic test in neurodevelopmental disorders in the USA since 2011. The impact of CMA results on clinical practice in China is not yet well studied, so we aimed to better evaluate this phenomenon.We analyzed the CMA results from 434 patients in our clinic, and characterized their molecular diagnoses, clinical features, and follow-up clinical actions based on these results. The overall diagnostic yield for our patients was 13.6%(59 out of 434). This gave a detection rate of 14.7%for developmental delay/intellectual disability(DD/ID,38/259) and 12% for autism spectrum disorders(ASDs,21/175). Thirty-three recurrent(n≥2) variants were found, distributed at six chromosomal loci involving known chromosome syndromes(such as DiGeorge, Williams Beuren, and Angelman/Prader-Willi syndromes).The spectrum of positive copy number variants in our study was comparable to that reported in Caucasian populations, but with specific characteristics. Parental origin tests indicated an effect involving a significant maternal transmission bias to sons. The majority of patients with positive results(94.9%) had benefits, allowing earlier diagnosis(36/59), prioritized full clinical management(28/59), medication changes(7/59), a changed prognosis(30/59), and prenatal genetic counseling(15/59). Our results provide information on de novo mutations in Chinese children with DD/ID and/or ASDs. Our data showed that microarray testing provides immediate clinical utility for patients. It is expected that the personalized medical care of children with developmental disabilities will lead to improved outcomes in long-term developmental potential.We advocate using the diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility.
