Sporadic late-onset Alzheimer’s disease(SLOAD)and familial early-onset Alzheimer’s disease(FEOAD)associated with dominant mutations in APP,PSEN1 and PSEN2,are thought to represent a spectrum of the same disorder bas...Sporadic late-onset Alzheimer’s disease(SLOAD)and familial early-onset Alzheimer’s disease(FEOAD)associated with dominant mutations in APP,PSEN1 and PSEN2,are thought to represent a spectrum of the same disorder based on near identical behavioral and histopathological features.Hence,FEOAD transgenic mouse models have been used in past decades as a surrogate to study SLOAD pathogenic mechanisms and as the gold standard to validate drugs used in clinical trials.Unfortunately,such research has yielded little output in terms of therapeutics targeting the disease’s development and progression.In this short review,we interrogate the widely accepted view of one,dimorphic disease through the prism of the Bmi1+/–mouse model and the distinct chromatin signatures observed between SLOAD and FEOAD brains.展开更多
Background： Proteasome subunits （PSMB） and transporter associated with antigen processing （TAP） loci are located in the human leukocyte antigen （HLA） Class I1 region play important roles in immune response and ...Background： Proteasome subunits （PSMB） and transporter associated with antigen processing （TAP） loci are located in the human leukocyte antigen （HLA） Class I1 region play important roles in immune response and protein degradation in neurodegenerative diseases. This study aimed to explore the association between single nucleotide polymorphisms （SNPs） of PSMB and TAP and Parkinson＇s disease （PD）. Methods： A case-control study was conducted by genotyping SNPs in PSMB8, PSMBg, TAP1, and TAP2 genes in the Chinese population. Subjects included 542 sporadic patients with PD and 674 healthy controls. Nine identified SNPs in PSMB8, PSMBg, TAP1, and TAP2 were genotyped through SNaPshot testing. Results： The stratified analysis ofrs 17587 was specially performed on gender. Data revealed that female patients carry a higher frequency of rsl7587-G/G versus （A/A ＋ G/A） compared with controls. But there was no significant difference with respect to the genotypic frequencies of the SNPs in PSMB8, TAP1, and TAP2 loci in PD patients. Conclusion： Chinese females carrying the rs 17587-G/G genotype in PSMB9 may increase a higher risk for PD, but no linkage was found between other SNPs in HLA Class II region and PD.展开更多
基金This work was supported by grants from the National Science and Engineering Research Council of Canada(NSERC)(to GB),Canadian Institutes of Health Research(CIHR)(to GB),Maisonneuve-Rosemont Hospital Foundation and Fondation de la Famille Pierre Theroux(to GB).RH is supported by a fellowship from the Maisonneuve-Rosemont Hospital Foundation.AF is supported by post-doctoral fellowship from the Jane Coffin Childs Fund.
文摘Sporadic late-onset Alzheimer’s disease(SLOAD)and familial early-onset Alzheimer’s disease(FEOAD)associated with dominant mutations in APP,PSEN1 and PSEN2,are thought to represent a spectrum of the same disorder based on near identical behavioral and histopathological features.Hence,FEOAD transgenic mouse models have been used in past decades as a surrogate to study SLOAD pathogenic mechanisms and as the gold standard to validate drugs used in clinical trials.Unfortunately,such research has yielded little output in terms of therapeutics targeting the disease’s development and progression.In this short review,we interrogate the widely accepted view of one,dimorphic disease through the prism of the Bmi1+/–mouse model and the distinct chromatin signatures observed between SLOAD and FEOAD brains.
基金Supplementary information is linked to the online version of the paper on the Chinese Medical Journal website.This work was supported by research grants from the National High Technology Research and Development Program of China （grant No. 2007AA02Z460）, the State Key Development Program for Basic Research of China （grant No. 2011CB510000）, the National Natural Science Foundation of China （grant No. 81271428, 81471292, U1503222, and 81430021） and the key point Science Foundation of Guangdong of China （No. 2015A030311021）, a grant supported by technology project of Guangzhou （No. 20151260） and a grant supported by assisting research project of science and technology for Xinjiang （No. 201591160）.
文摘Background： Proteasome subunits （PSMB） and transporter associated with antigen processing （TAP） loci are located in the human leukocyte antigen （HLA） Class I1 region play important roles in immune response and protein degradation in neurodegenerative diseases. This study aimed to explore the association between single nucleotide polymorphisms （SNPs） of PSMB and TAP and Parkinson＇s disease （PD）. Methods： A case-control study was conducted by genotyping SNPs in PSMB8, PSMBg, TAP1, and TAP2 genes in the Chinese population. Subjects included 542 sporadic patients with PD and 674 healthy controls. Nine identified SNPs in PSMB8, PSMBg, TAP1, and TAP2 were genotyped through SNaPshot testing. Results： The stratified analysis ofrs 17587 was specially performed on gender. Data revealed that female patients carry a higher frequency of rsl7587-G/G versus （A/A ＋ G/A） compared with controls. But there was no significant difference with respect to the genotypic frequencies of the SNPs in PSMB8, TAP1, and TAP2 loci in PD patients. Conclusion： Chinese females carrying the rs 17587-G/G genotype in PSMB9 may increase a higher risk for PD, but no linkage was found between other SNPs in HLA Class II region and PD.
