Tripeptidyl Peptidase(三肽基肽酶)研究综述
Tripeptidyl Peptidase 三肽基肽酶 - Tripeptidyl peptidase-1 offered a predictive value for outcome, with an area under a ROC curve of 84. [1] We created multiple cell lines each with different levels of reduction of expression of the gene coding for the type 2 variant of the disease, Tripeptidyl peptidase (Tpp1), in the cellular slime mould Dictyostelium discoideum. [2]Tripeptidyl peptidase-1 为结果提供了预测价值，ROC 曲线下面积为 84。 [1] 我们在细胞粘液霉菌盘基网柄菌中创建了多个细胞系，每个细胞系的编码该疾病的 2 型变体三肽基肽酶 (Tpp1) 的基因表达降低程度不同。 [2]
enzyme replacement therapy 酶替代疗法
Cerliponase alfa is recombinant human tripeptidyl peptidase 1 enzyme replacement therapy. [1] In 2017, cerliponase alfa (Brineura), a tripeptidyl peptidase enzyme replacement therapy, became the first globally approved treatment for CLN2 Batten disease. [2] Abbreviations: AIF1/IBA1: allograft inflammatory factor 1; BBB: blood brain barrier; CNS: central nervous system; CTSB: cathepsin B; CTSD: cathepsin D; CTSL: cathepsin L; ERT: enzyme replacement therapy; GFAP: glial fibrillary acidic protein; INL: inner nuclear layer; LAMP1: lysosomal-associated membrane protein 1; LAMP2: lysosomal-associated membrane protein 2; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; LDL: low-density lipoprotein; LRP1: low density lipoprotein receptor-related protein 1; LSD: lysosomal storage disorder; MEFs: mouse embryonic fibroblasts; M6P: mannose 6-phosphate; mCTSD: mature CTSD; NCL: neuronal ceroid lipofuscinosis; ONL: outer nuclear layer; PB: phosphate buffer; proCTSD: pro-cathepsin D; LRPAP1: low density lipoprotein receptor-related protein associated protein 1; rhCTSD: human recombinant CTSD; SAPC: saposin C; SAPD: saposin D; ATP5G1: ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C1 (subunit 9); SQSTM1/p62: sequestosome 1; TPP1: tripeptidyl peptidase I. [3]Cerliponase alfa 是重组人三肽基肽酶 1 酶替代疗法。 [1] 2017年，三肽基肽酶替代疗法cerliponase alfa (Brineura)成为全球首个获批的CLN2 Batten病治疗药物。 [2] nan [3]
lysosomal storage disorder 溶酶体贮积症
The late-infantile Batten disease or late-infantile neuronal ceroid lipofuscinosis (LINCL) is an autosomal recessive lysosomal storage disorder caused by mutations in the Cln2 gene leading to deficiency of lysosomal enzyme tripeptidyl peptidase 1 (TPP1). [1] Herein, the use of macrophage-derived EVs for brain delivery of a soluble lysosomal enzyme tripeptidyl peptidase-1, TPP1, to treat a lysosomal storage disorder, Neuronal Ceroid Lipofuscinoses 2 (CLN2) or Batten disease, is investigated. [2]婴儿晚期巴顿病或婴儿晚期神经元蜡样脂褐质沉积症 (LINCL) 是一种常染色体隐性遗传溶酶体贮积症，由导致溶酶体酶三肽基肽酶 1 (TPP1) 缺乏的 Cln2 基因突变引起。 [1] 在此，研究了使用巨噬细胞衍生的 EV 向大脑输送可溶性溶酶体酶三肽基肽酶 TPP1，以治疗溶酶体贮积症、神经元蜡样脂褐质 2 (CLN2) 或巴顿病。 [2]
lysosomal associated membrane 溶酶体相关膜
Abbreviations: ALS: amyotrophic lateral sclerosis; AR: androgen receptor; ATG: autophagy related; AV: autophagic vacuole; BAG3: BCL2-associated athanogene 3; BECN1: beclin 1, autophagy related; CASA: chaperone-assisted selective autophagy; CTSB: cathepsin b; DAPI: 4ʹ,6-diamidino-2-phenylindole; DMEM: Dulbecco’s modified Eagle’s medium; EGFP: enhanced green fluorescent protein; fALS, familial amyotrophic lateral sclerosis; FRA: filter retardation assay; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GLA: galactosidase, alpha; HD: Huntington disease; hIPSCs: human induced pluripotent stem cells; HSPA8: heat shock protein A8; HSPB8: heat shock protein B8; IF: immunofluorescence analysis; LAMP1: lysosomal-associated membrane protein 1; LAMP2A: lysosomal-associated membrane protein 2A; LGALS3: lectin, galactose binding, soluble 3; LLOMe: L-leucyl-L-leucine methyl ester; LMP: lysosomal membrane permeabilization; Lys: lysosomes; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MCOLN1: mucolipin 1; mRNA: messenger RNA; MTOR: mechanistic target of rapamycin kinase; NDs: neurodegenerative diseases; NSC34: neuroblastoma x spinal cord 34; PBS: phosphate-buffered saline; PD: Parkinson disease; polyQ: polyglutamine; PPARGC1A: peroxisome proliferative activated receptor, gamma, coactivator 1 alpha; PPP3CB: protein phosphatase 3, catalytic subunit, beta isoform; RT-qPCR: real-time quantitative polymerase chain reaction; SBMA: spinal and bulbar muscular atrophy; SCAs: spinocerebellar ataxias; siRNA: small interfering RNA; SLC2A8: solute carrier family 2, (facilitated glucose transporter), member 8; smNPCs: small molecules neural progenitors cells; SOD1: superoxide dismutase 1; SQSTM1/p62: sequestosome 1; STED: stimulated emission depletion; STUB1: STIP1 homology and U-box containing protein 1; TARDBP/TDP-43: TAR DNA binding protein; TFEB: transcription factor EB; TPP1: tripeptidyl peptidase I; TREH: trehalase (brush-border membrane glycoprotein); WB: western blotting; ZKSCAN3: zinc finger with KRAB and SCAN domains 3. [1]缩写：ALS：肌萎缩侧索硬化； AR：雄激素受体； ATG：自噬相关； AV：自噬泡； BAG3：BCL2 相关的 athanogene 3； BECN1：beclin 1，自噬相关； CASA：伴侣辅助选择性自噬； CTSB：组织蛋白酶 b； DAPI：4ʹ,6-二脒基-2-苯基吲哚； DMEM：Dulbecco改良Eagle培养基； EGFP：增强型绿色荧光蛋白； fALS，家族性肌萎缩侧索硬化症； FRA：过滤器阻滞试验； GAPDH：3-磷酸甘油醛脱氢酶； GLA：半乳糖苷酶，α；高清：亨廷顿病； hIPSCs：人类诱导的多能干细胞； HSPA8：热休克蛋白A8； HSPB8：热休克蛋白 B8； IF：免疫荧光分析； LAMP1：溶酶体相关膜蛋白 1； LAMP2A：溶酶体相关膜蛋白 2A； LGALS3：凝集素，半乳糖结合，可溶性3； LLOMe：L-亮氨酰-L-亮氨酸甲酯； LMP：溶酶体膜透化； Lys：溶酶体； MAP1LC3B：微管相关蛋白 1 轻链 3 β； MCOLN1：粘磷脂1； mRNA：信使RNA； MTOR：雷帕霉素激酶的机制靶点； ND：神经退行性疾病； NSC34：神经母细胞瘤 x 脊髓 34； PBS：磷酸盐缓冲液； PD：帕金森病； polyQ：聚谷氨酰胺； PPARGC1A：过氧化物酶体增殖激活受体，γ，辅激活因子 1 α； PPP3CB：蛋白磷酸酶 3，催化亚基，β 异构体； RT-qPCR：实时定量聚合酶链反应； SBMA：脊髓和延髓肌萎缩； SCA：脊髓小脑共济失调； siRNA：小干扰RNA； SLC2A8：溶质载体家族 2，（促进葡萄糖转运蛋白），成员 8； smNPCs：小分子神经祖细胞； SOD1：超氧化物歧化酶1； SQSTM1/p62：隔离体 1； STED：受激发射损耗； STUB1：STIP1同源性和含有蛋白1的U-box； TARDBP/TDP-43：TAR DNA 结合蛋白； TFEB：转录因子EB； TPP1：三肽基肽酶 I； TRH：海藻糖酶（刷状缘膜糖蛋白）； WB：蛋白质印迹； ZKSCAN3：具有 KRAB 和 SCAN 结构域 3 的锌指。 [1]
Enzyme Tripeptidyl Peptidase 酶三肽基肽酶
The late-infantile Batten disease or late-infantile neuronal ceroid lipofuscinosis (LINCL) is an autosomal recessive lysosomal storage disorder caused by mutations in the Cln2 gene leading to deficiency of lysosomal enzyme tripeptidyl peptidase 1 (TPP1). [1] It is caused by a deficiency of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). [2] Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare, progressive, fatal neurodegenerative pediatric disorder resulting from deficiencies of the lysosomal enzyme tripeptidyl peptidase 1 that are caused by mutations in TPP1. [3] PURPOSE CLN2 disease is a genetic disorder caused by dysfunction of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1) that belongs to the neuronal ceroid lipofuscinoses (NCL) and leads to epilepsy, dementia, and death in young persons. [4] Neuronal ceroid lipofuscinoses type 2 disease (CLN2) is a very rare, autosomal recessive neurodegerative disease caused by deficient activity of the enzyme tripeptidyl peptidase 1 (TPP1). [5] Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is an autosomal recessive condition caused by variants in the TPP1 gene, leading to deficient activity of the lysosomal enzyme tripeptidyl peptidase I (TPP1). [6] Herein, the use of macrophage-derived EVs for brain delivery of a soluble lysosomal enzyme tripeptidyl peptidase-1, TPP1, to treat a lysosomal storage disorder, Neuronal Ceroid Lipofuscinoses 2 (CLN2) or Batten disease, is investigated. [7]婴儿晚期巴顿病或婴儿晚期神经元蜡样脂褐质沉积症 (LINCL) 是一种常染色体隐性遗传溶酶体贮积症，由导致溶酶体酶三肽基肽酶 1 (TPP1) 缺乏的 Cln2 基因突变引起。 [1] 它是由溶酶体酶三肽基肽酶 1 (TPP1) 的缺乏引起的。 [2] nan [3] nan [4] nan [5] 神经元蜡样脂褐质沉着症 2 型（CLN2 病）是一种常染色体隐性遗传病，由 TPP1 基因变异引起，导致溶酶体酶三肽基肽酶 I (TPP1) 活性不足。 [6] 在此，研究了使用巨噬细胞衍生的 EV 向大脑输送可溶性溶酶体酶三肽基肽酶 TPP1，以治疗溶酶体贮积症、神经元蜡样脂褐质 2 (CLN2) 或巴顿病。 [7]
tripeptidyl peptidase 1 三肽基肽酶 1
Cerliponase alfa is recombinant human tripeptidyl peptidase 1 enzyme replacement therapy. [1] Results Enzymatic analysis of palmitoyl protein thioesterase 1 (PPT1)and tripeptidyl peptidase 1(TPP1) enzymes was within normal level in the four patients. [2] The late-infantile Batten disease or late-infantile neuronal ceroid lipofuscinosis (LINCL) is an autosomal recessive lysosomal storage disorder caused by mutations in the Cln2 gene leading to deficiency of lysosomal enzyme tripeptidyl peptidase 1 (TPP1). [3] In humans, homozygous mutations in the TPP1 gene results in loss of tripeptidyl peptidase 1 (TPP1) enzymatic activity, leading to late infantile neuronal ceroid lipofuscinoses disease. [4] The serine aminopeptidase, tripeptidyl peptidase 1 (TPP1), was detected by proteomic analysis of cyst fluid samples and quantitation using targeted MS demonstrated that this protease was significantly more abundant in mucinous cysts. [5] Six compounds enhanced mitochondrial transport in the sub-micromolar range, acting via three cellular targets: F-actin, Tripeptidyl peptidase 1 (TPP1), or Aurora Kinase B (AurKB). [6] It is caused by a deficiency of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). [7] Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare, progressive, fatal neurodegenerative pediatric disorder resulting from deficiencies of the lysosomal enzyme tripeptidyl peptidase 1 that are caused by mutations in TPP1. [8] PURPOSE CLN2 disease is a genetic disorder caused by dysfunction of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1) that belongs to the neuronal ceroid lipofuscinoses (NCL) and leads to epilepsy, dementia, and death in young persons. [9] We investigated the role of the lysosomal protease tripeptidyl peptidase 1 (TPP1) in cell culture and in a mouse model of Alzheimer’s disease. [10] Neuronal ceroid lipofuscinoses type 2 disease (CLN2) is a very rare, autosomal recessive neurodegerative disease caused by deficient activity of the enzyme tripeptidyl peptidase 1 (TPP1). [11] described first symptoms in CLN2 disease, which is caused by mutations in the tripeptidyl peptidase 1 (TPP1)/CLN2 gene, resulting in TPP1 enzyme deficiency and subsequent lysosomal storage. [12]Cerliponase alfa 是重组人三肽基肽酶 1 酶替代疗法。 [1] 结果 4例患者的棕榈酰蛋白硫酯酶1（PPT1）和三肽基肽酶1（TPP1）酶学分析均在正常水平。 [2] 婴儿晚期巴顿病或婴儿晚期神经元蜡样脂褐质沉积症 (LINCL) 是一种常染色体隐性遗传溶酶体贮积症，由导致溶酶体酶三肽基肽酶 1 (TPP1) 缺乏的 Cln2 基因突变引起。 [3] 在人类中，TPP1 基因的纯合突变导致三肽基肽酶 1 (TPP1) 酶活性丧失，从而导致晚期婴儿神经元蜡样脂褐质病。 [4] 通过对囊液样品的蛋白质组学分析检测到丝氨酸氨基肽酶三肽基肽酶 1 (TPP1)，使用靶向 MS 进行定量表明该蛋白酶在粘液性囊肿中的含量明显更高。 [5] 六种化合物通过三个细胞靶点增强亚微摩尔范围内的线粒体转运：F-肌动蛋白、三肽基肽酶 1 (TPP1) 或极光激酶 B (AurKB)。 [6] 它是由溶酶体酶三肽基肽酶 1 (TPP1) 的缺乏引起的。 [7] nan [8] nan [9] nan [10] nan [11] 描述了 CLN2 疾病的首发症状，这是由三肽基肽酶 1 (TPP1)/CLN2 基因突变引起的，导致 TPP1 酶缺乏和随后的溶酶体储存。 [12]
tripeptidyl peptidase i 三肽基肽酶 I
Abbreviations: ALS: amyotrophic lateral sclerosis; AR: androgen receptor; ATG: autophagy related; AV: autophagic vacuole; BAG3: BCL2-associated athanogene 3; BECN1: beclin 1, autophagy related; CASA: chaperone-assisted selective autophagy; CTSB: cathepsin b; DAPI: 4ʹ,6-diamidino-2-phenylindole; DMEM: Dulbecco’s modified Eagle’s medium; EGFP: enhanced green fluorescent protein; fALS, familial amyotrophic lateral sclerosis; FRA: filter retardation assay; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GLA: galactosidase, alpha; HD: Huntington disease; hIPSCs: human induced pluripotent stem cells; HSPA8: heat shock protein A8; HSPB8: heat shock protein B8; IF: immunofluorescence analysis; LAMP1: lysosomal-associated membrane protein 1; LAMP2A: lysosomal-associated membrane protein 2A; LGALS3: lectin, galactose binding, soluble 3; LLOMe: L-leucyl-L-leucine methyl ester; LMP: lysosomal membrane permeabilization; Lys: lysosomes; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MCOLN1: mucolipin 1; mRNA: messenger RNA; MTOR: mechanistic target of rapamycin kinase; NDs: neurodegenerative diseases; NSC34: neuroblastoma x spinal cord 34; PBS: phosphate-buffered saline; PD: Parkinson disease; polyQ: polyglutamine; PPARGC1A: peroxisome proliferative activated receptor, gamma, coactivator 1 alpha; PPP3CB: protein phosphatase 3, catalytic subunit, beta isoform; RT-qPCR: real-time quantitative polymerase chain reaction; SBMA: spinal and bulbar muscular atrophy; SCAs: spinocerebellar ataxias; siRNA: small interfering RNA; SLC2A8: solute carrier family 2, (facilitated glucose transporter), member 8; smNPCs: small molecules neural progenitors cells; SOD1: superoxide dismutase 1; SQSTM1/p62: sequestosome 1; STED: stimulated emission depletion; STUB1: STIP1 homology and U-box containing protein 1; TARDBP/TDP-43: TAR DNA binding protein; TFEB: transcription factor EB; TPP1: tripeptidyl peptidase I; TREH: trehalase (brush-border membrane glycoprotein); WB: western blotting; ZKSCAN3: zinc finger with KRAB and SCAN domains 3. [1] Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is an autosomal recessive condition caused by variants in the TPP1 gene, leading to deficient activity of the lysosomal enzyme tripeptidyl peptidase I (TPP1). [2] Abbreviations: AIF1/IBA1: allograft inflammatory factor 1; BBB: blood brain barrier; CNS: central nervous system; CTSB: cathepsin B; CTSD: cathepsin D; CTSL: cathepsin L; ERT: enzyme replacement therapy; GFAP: glial fibrillary acidic protein; INL: inner nuclear layer; LAMP1: lysosomal-associated membrane protein 1; LAMP2: lysosomal-associated membrane protein 2; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; LDL: low-density lipoprotein; LRP1: low density lipoprotein receptor-related protein 1; LSD: lysosomal storage disorder; MEFs: mouse embryonic fibroblasts; M6P: mannose 6-phosphate; mCTSD: mature CTSD; NCL: neuronal ceroid lipofuscinosis; ONL: outer nuclear layer; PB: phosphate buffer; proCTSD: pro-cathepsin D; LRPAP1: low density lipoprotein receptor-related protein associated protein 1; rhCTSD: human recombinant CTSD; SAPC: saposin C; SAPD: saposin D; ATP5G1: ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C1 (subunit 9); SQSTM1/p62: sequestosome 1; TPP1: tripeptidyl peptidase I. [3]缩写：ALS：肌萎缩侧索硬化； AR：雄激素受体； ATG：自噬相关； AV：自噬泡； BAG3：BCL2 相关的 athanogene 3； BECN1：beclin 1，自噬相关； CASA：伴侣辅助选择性自噬； CTSB：组织蛋白酶 b； DAPI：4ʹ,6-二脒基-2-苯基吲哚； DMEM：Dulbecco改良Eagle培养基； EGFP：增强型绿色荧光蛋白； fALS，家族性肌萎缩侧索硬化症； FRA：过滤器阻滞试验； GAPDH：3-磷酸甘油醛脱氢酶； GLA：半乳糖苷酶，α；高清：亨廷顿病； hIPSCs：人类诱导的多能干细胞； HSPA8：热休克蛋白A8； HSPB8：热休克蛋白 B8； IF：免疫荧光分析； LAMP1：溶酶体相关膜蛋白 1； LAMP2A：溶酶体相关膜蛋白 2A； LGALS3：凝集素，半乳糖结合，可溶性3； LLOMe：L-亮氨酰-L-亮氨酸甲酯； LMP：溶酶体膜透化； Lys：溶酶体； MAP1LC3B：微管相关蛋白 1 轻链 3 β； MCOLN1：粘磷脂1； mRNA：信使RNA； MTOR：雷帕霉素激酶的机制靶点； ND：神经退行性疾病； NSC34：神经母细胞瘤 x 脊髓 34； PBS：磷酸盐缓冲液； PD：帕金森病； polyQ：聚谷氨酰胺； PPARGC1A：过氧化物酶体增殖激活受体，γ，辅激活因子 1 α； PPP3CB：蛋白磷酸酶 3，催化亚基，β 异构体； RT-qPCR：实时定量聚合酶链反应； SBMA：脊髓和延髓肌萎缩； SCA：脊髓小脑共济失调； siRNA：小干扰RNA； SLC2A8：溶质载体家族 2，（促进葡萄糖转运蛋白），成员 8； smNPCs：小分子神经祖细胞； SOD1：超氧化物歧化酶1； SQSTM1/p62：隔离体 1； STED：受激发射损耗； STUB1：STIP1同源性和含有蛋白1的U-box； TARDBP/TDP-43：TAR DNA 结合蛋白； TFEB：转录因子EB； TPP1：三肽基肽酶 I； TRH：海藻糖酶（刷状缘膜糖蛋白）； WB：蛋白质印迹； ZKSCAN3：具有 KRAB 和 SCAN 结构域 3 的锌指。 [1] 神经元蜡样脂褐质沉着症 2 型（CLN2 病）是一种常染色体隐性遗传病，由 TPP1 基因变异引起，导致溶酶体酶三肽基肽酶 I (TPP1) 活性不足。 [2] nan [3]