Parkinson’s disease is the second most common neurodegenerative disorder.ATPase H+transporting V0 subunit A1(ATP6V0A1)is a component of vacuolar H+-ATPase(V-ATPase),an ATP-dependent proton pump.Our previous research ...Parkinson’s disease is the second most common neurodegenerative disorder.ATPase H+transporting V0 subunit A1(ATP6V0A1)is a component of vacuolar H+-ATPase(V-ATPase),an ATP-dependent proton pump.Our previous research identified an association between the ATP6V0A1 rs601999 variant and Parkinson’s disease;however,the underlying mechanisms of ATP6V0A1 in Parkinson’s disease remain elusive.In this study,we generated ATP6V0A1 knockdown and overexpression models and then examined the degeneration of dopaminergic neurons,lysosomal function,and the autophagy-lysosomal pathway using immunohistochemistry,western blotting,and transmission electron microscopy.We found that ATP6V0A1 protected against lysosomal dysfunction,regulated autophagic flux,and decreased phosphorylatedα-synuclein levels in vitro.In vivo,ATP6V0A1 reduced levels ofα-synuclein and phosphorylatedα-synuclein proteins,mitigated degeneration of dopaminergic neurons,and improved motor dysfunction.Collectively,these findings show that ATP6V0A1 plays a protective role in Parkinson’s disease by modulating the autophagy-lysosomal pathway.A correlation between ATP6V0A1 and Parkinson’s disease susceptibility may serve as a biomarker for Parkinson’s disease,while the protective effects of ATP6V0A1 could represent a potential therapeutic target for the disease.展开更多
发育性和癫痫性脑病93(Developmental and epileptic encephalopathy 93,DEE93)(MIM:618012)是一种常染色体显性遗传神经系统疾病,主要特点为精神运动发育迟缓、早发难治性癫痫和智力低下等,且与ATP6V1A基因变异有关^([1])。DEE93临床...发育性和癫痫性脑病93(Developmental and epileptic encephalopathy 93,DEE93)(MIM:618012)是一种常染色体显性遗传神经系统疾病,主要特点为精神运动发育迟缓、早发难治性癫痫和智力低下等,且与ATP6V1A基因变异有关^([1])。DEE93临床表现差异大,病情轻重不一,重者可因快速进展的早期致命性脑病而死亡,轻者仅表现为轻度至中度智力障碍,伴或不伴癫痫发作^([2-3])。ATP6V1A基因(MIM#607027)染色体位置为3q13.3,包含15个外显子,编码617个氨基酸,是组成ATP酶(V-ATPase)的一个亚基,参与介导真核细胞内的质子运输过程和细胞器的酸化。本文报告了1例全外显子测序发现ATP6V1A基因杂合致病性变异c.937G>C:p.Ala313Pro的婴儿,描述了其临床表现并复习相关文献内容,扩展了ATP6V1A基因突变相关DEE93的临床特征和遗传谱,为该病的诊断、治疗和遗传咨询提供参考。展开更多
Bet v 1基因家族编码植物病程相关蛋白PR10,参与植物的非生物和生物胁迫应答。本研究对新疆沙冬青Bet v 1基因家族进行筛选和进化分析,并通过实时荧光定量PCR分析了Bet v 1基因在低温和渗透胁迫下的表达模式。结果表明筛选到27个新疆沙...Bet v 1基因家族编码植物病程相关蛋白PR10,参与植物的非生物和生物胁迫应答。本研究对新疆沙冬青Bet v 1基因家族进行筛选和进化分析,并通过实时荧光定量PCR分析了Bet v 1基因在低温和渗透胁迫下的表达模式。结果表明筛选到27个新疆沙冬青Bet v 1基因家族成员,均包含内含子,分布于6条染色体上。在新疆沙冬青中有11个Bet v 1基因在大豆、拟南芥基因组中具有直系同源基因。该基因家族成员的启动子中含有大量与逆境胁迫和激素响应相关的元件。基因表达分析显示EVM0015604.1、EVM0020624.1、EVM000-0761.1、EVM0033568.1和EVM0004485.1的表达量在低温和渗透胁迫下升高,推测Bet v 1基因参与了新疆沙冬青响应低温和干旱胁迫。本研究为理解植物Bet v 1基因的功能提供了一定的理论依据。展开更多
基金supported by the Youth Program of the National Natural Science Foundation of China,Nos.81901282(to XC),82101326(to WG),81870992(to PX),and 81870856the Guangdong Basic and Applied Basic Research Foundation of the Science Foundation,Nos.2024A1515012919(to XC)and 2019A1515011189(to XC)+5 种基金the Central Government Guiding Local Science and Technology Development Projects,No.ZYYD2022C17(to PX)the Key Project of the Guangzhou Health Commission,No.2019-ZD-09(to PX)the Basic and Applied Basic Research of the City and School Jointly Funded Projects,No.20220102397(to QL)the Guangdong College Students Innovation and Entrepreneurship Training Program,No.S202310570017(to WY)the Science and Technology Planning Project of Guangzhou,Nos.2023B03J0631(to PX),2024A03J1152(to XC),and 202102010010(to PX)the Basic Research Program of the Guangzhou Science and Technology Bureau Jointly-funded Dengfeng Hospital Project,No.20232031(to XC).
文摘Parkinson’s disease is the second most common neurodegenerative disorder.ATPase H+transporting V0 subunit A1(ATP6V0A1)is a component of vacuolar H+-ATPase(V-ATPase),an ATP-dependent proton pump.Our previous research identified an association between the ATP6V0A1 rs601999 variant and Parkinson’s disease;however,the underlying mechanisms of ATP6V0A1 in Parkinson’s disease remain elusive.In this study,we generated ATP6V0A1 knockdown and overexpression models and then examined the degeneration of dopaminergic neurons,lysosomal function,and the autophagy-lysosomal pathway using immunohistochemistry,western blotting,and transmission electron microscopy.We found that ATP6V0A1 protected against lysosomal dysfunction,regulated autophagic flux,and decreased phosphorylatedα-synuclein levels in vitro.In vivo,ATP6V0A1 reduced levels ofα-synuclein and phosphorylatedα-synuclein proteins,mitigated degeneration of dopaminergic neurons,and improved motor dysfunction.Collectively,these findings show that ATP6V0A1 plays a protective role in Parkinson’s disease by modulating the autophagy-lysosomal pathway.A correlation between ATP6V0A1 and Parkinson’s disease susceptibility may serve as a biomarker for Parkinson’s disease,while the protective effects of ATP6V0A1 could represent a potential therapeutic target for the disease.
文摘发育性和癫痫性脑病93(Developmental and epileptic encephalopathy 93,DEE93)(MIM:618012)是一种常染色体显性遗传神经系统疾病,主要特点为精神运动发育迟缓、早发难治性癫痫和智力低下等,且与ATP6V1A基因变异有关^([1])。DEE93临床表现差异大,病情轻重不一,重者可因快速进展的早期致命性脑病而死亡,轻者仅表现为轻度至中度智力障碍,伴或不伴癫痫发作^([2-3])。ATP6V1A基因(MIM#607027)染色体位置为3q13.3,包含15个外显子,编码617个氨基酸,是组成ATP酶(V-ATPase)的一个亚基,参与介导真核细胞内的质子运输过程和细胞器的酸化。本文报告了1例全外显子测序发现ATP6V1A基因杂合致病性变异c.937G>C:p.Ala313Pro的婴儿,描述了其临床表现并复习相关文献内容,扩展了ATP6V1A基因突变相关DEE93的临床特征和遗传谱,为该病的诊断、治疗和遗传咨询提供参考。
文摘Bet v 1基因家族编码植物病程相关蛋白PR10,参与植物的非生物和生物胁迫应答。本研究对新疆沙冬青Bet v 1基因家族进行筛选和进化分析,并通过实时荧光定量PCR分析了Bet v 1基因在低温和渗透胁迫下的表达模式。结果表明筛选到27个新疆沙冬青Bet v 1基因家族成员,均包含内含子,分布于6条染色体上。在新疆沙冬青中有11个Bet v 1基因在大豆、拟南芥基因组中具有直系同源基因。该基因家族成员的启动子中含有大量与逆境胁迫和激素响应相关的元件。基因表达分析显示EVM0015604.1、EVM0020624.1、EVM000-0761.1、EVM0033568.1和EVM0004485.1的表达量在低温和渗透胁迫下升高,推测Bet v 1基因参与了新疆沙冬青响应低温和干旱胁迫。本研究为理解植物Bet v 1基因的功能提供了一定的理论依据。
