溶酶体酶PPT1介导的细胞稳态调控及疾病发生的研究进展

doi:10.16288/j.yczz.23-186

遗传 ›› 2023, Vol. 45 ›› Issue (10): 874-886.doi: 10.16288/j.yczz.23-186

溶酶体酶PPT1介导的细胞稳态调控及疾病发生的研究进展

周欣怡(), 常栋(), 徐黄莹, 关瑞琪, 严程浩, 尹秋媛(), 孙建伟()

云南大学生命科学中心、云南省细胞代谢与疾病重点实验室、省部共建云南生物资源保护与利用国家重点实验室，生命科学学院，昆明 650500

收稿日期:2023-07-07 修回日期:2023-09-19 出版日期:2023-10-20 发布日期:2023-09-28
通讯作者: 尹秋媛,孙建伟 E-mail:1295351648@qq.com;13648831440@139.com;jwsun@ynu.edu.cn;qiuyuan_yin@ynu.edu.cn
作者简介:周欣怡，硕士研究生，专业方向：肿瘤转移与发生机制。E-mail: 1295351648@qq.com;|常栋，硕士研究生，专业方向：肿瘤转移与发生机制。E-mail: 13648831440@139.com;
周欣怡和常栋并列第一作者。
基金资助:
国家自然科学基金(82273460);国家自然科学基金(32260167);云南大学研究生科研创新项目(ZC-22223017);云南大学研究生科研创新项目(ZC-22223104)

Progress on lysosomal PPT1-mediated regulation of cellular homeostasis and pathogenesis

Xinyi Zhou(), Dong Chang(), Huangying Xu, Ruiqi Guan, Chenghao Yan, Qiuyuan Yin(), Jianwei Sun()

Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650500 China

Received:2023-07-07 Revised:2023-09-19 Published:2023-10-20 Online:2023-09-28
Contact: Qiuyuan Yin,Jianwei Sun E-mail:1295351648@qq.com;13648831440@139.com;jwsun@ynu.edu.cn;qiuyuan_yin@ynu.edu.cn
Supported by:
National Natural Science Foundation of China(82273460);National Natural Science Foundation of China(32260167);Yunnan University Graduate Research Innovation Project(ZC-22223017);Yunnan University Graduate Research Innovation Project(ZC-22223104)

摘要/Abstract

摘要：

棕榈酰蛋白质硫酯酶1 (palmitoyl protein thioesterase 1，PPT1)是一种溶酶体酶，具有对蛋白质行使去棕榈酰化修饰的功能，在调控细胞器(如溶酶体、线粒体)功能、脂质代谢和Ca²⁺转运等方面具有重要作用。PPT1在神经系统疾病和癌症的发生发展中发挥了重要的作用，然而其调控作用机制仍未被完全阐明。本文综述了目前PPT1在脂质代谢调控、物质转运调控、钙稳态调控过程中的作用及最新研究进展，总结并探讨了PPT1在神经系统疾病及肿瘤发生发展中作用及调控机制，为将来更深层次研究PPT1的功能及调控机制并开发相关疾病治疗的新药物提供借鉴和参考。

关键词: 棕榈酰蛋白质硫酯酶1, 去棕榈酰化, 溶酶体, 疾病发生

Abstract:

Palmitoyl protein thioesterase 1(PPT1) is a lysosomal enzyme that catalyzes the protein depalmitoylation. It is considered to play a crucial role in regulating lysosomes, mitochondria and lipid metabolism. PPT1 has been reported to play an important role in the occurrence and progression of diseases, such as neurological diseases and cancers. However, the regulatory mechanisms remain unknown. In this review, we summarize the progress of PPT1 function and mechanisms in neurological disorders and cancers, which will provide as reference and guidance for exploring the regulatory mechanisms of PPT1 and developing new drugs for treating related diseases in the future.

Key words: Palmitoyl protein thioesterase 1, depalmitoylation, lysosome, disease

周欣怡, 常栋, 徐黄莹, 关瑞琪, 严程浩, 尹秋媛, 孙建伟. 溶酶体酶PPT1介导的细胞稳态调控及疾病发生的研究进展[J]. 遗传, 2023, 45(10): 874-886.

Xinyi Zhou, Dong Chang, Huangying Xu, Ruiqi Guan, Chenghao Yan, Qiuyuan Yin, Jianwei Sun. Progress on lysosomal PPT1-mediated regulation of cellular homeostasis and pathogenesis[J]. Hereditas(Beijing), 2023, 45(10): 874-886.

图/表 4

图1

图2

图3

表1

参考文献 100

[1]	Camp LA, Hofmann SL. Purification and properties of a palmitoyl-protein thioesterase that cleaves palmitate from H-Ras. J Biol Chem, 1993, 268(30): 22566-22574. pmid: 7901201
[2]	Camp LA, Verkruyse LA, Afendis SJ, Slaughter CA, Hofmann SL. Molecular cloning and expression of palmitoyl-protein thioesterase. J Biol Chem, 1994, 269(37): 23212-23219. pmid: 7916016
[3]	Verkruyse LA, Hofmann SL. Lysosomal targeting of palmitoyl-protein thioesterase. J Biol Chem, 1996, 271(26): 15831-15836. doi: 10.1074/jbc.271.26.15831 pmid: 8663305
[4]	Hawkins-Salsbury JA, Cooper JD, Sands MS. Pathogenesis and therapies for infantile neuronal ceroid lipofuscinosis (infantile CLN1 disease). Biochim Biophys Acta, 2013, 1832(11): 1906-1909. doi: 10.1016/j.bbadis.2013.05.026 pmid: 23747979
[5]	Calero G, Gupta P, Nonato MC, Tandel S, Biehl ER, Hofmann SL, Clardy J.The crystal structure of palmitoyl protein thioesterase-2 (PPT2)reveals the basis for divergent substrate specificities of the two lysosomal thioesterases, PPT1 and PPT2. J Biol Chem, 2003, 278(39): 37957-37964. doi: 10.1074/jbc.M301225200
[6]	Kim SJ, Zhang ZJ, Sarkar C, Tsai PC, Lee YC, Dye L, Mukherjee AB. Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and mice. J Clin Invest, 2008, 118(9): 3075-3086. doi: 10.1172/JCI33482
[7]	Sharma G, Ojha R, Noguera-Ortega E, Rebecca VW, Attanasio J, Liu SJ, Piao SF, Lee JJ, Nicastri MC, Harper SL, Ronghe A, Jain V, Winkler JD, Speicher DW, Mastio J, Gimotty PA, Xu XW, Wherry EJ, Gabrilovich DI, Amaravadi RK. PPT1 inhibition enhances the antitumor activity of anti-PD-1 antibody in melanoma. JCI Insight, 2020, 5(17): e133225. doi: 10.1172/jci.insight.133225
[8]	Jalanko A, Vesa J, Manninen T, von Schantz C, Minye H, Fabritius AL, Salonen T, Rapola J, Gentile M, Kopra O, Peltonen L. Mice with Ppt1Deltaex4 mutation replicate the INCL phenotype and show an inflammation-associated loss of interneurons. Neurobiol Dis, 2005, 18(1): 226-241. pmid: 15649713
[9]	Tikka S, Monogioudi E, Gotsopoulos A, Soliymani R, Pezzini F, Scifo E, Uusi-Rauva K, Tyynelä J, Baumann M, Jalanko A, Simonati A, Lalowski M. Proteomic profiling in the brain of CLN1 disease model reveals affected functional modules. Neuromolecular Med, 2016, 18(1): 109-133. doi: 10.1007/s12017-015-8382-6
[10]	Zhao Y, Xu X, Wang Y, Wu LD, Luo RL, Xia RP. Tumor purity-associated genes influence hepatocellular carcinoma prognosis and tumor microenvironment. Front Oncol, 2023, 13: 1197898. doi: 10.3389/fonc.2023.1197898
[11]	Vesa J, Hellsten E, Verkruyse LA, Camp LA, Rapola J, Santavuori P, Hofmann SL, Peltonen L. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature, 1995, 376(6541): 584-587. doi: 10.1038/376584a0
[12]	Schriner JE, Yi W, Hofmann SL. cDNA and genomic cloning of human palmitoyl-protein thioesterase (PPT), the enzyme defective in infantile neuronal ceroid lipofuscinosis. Genomics, 1996, 34(3): 317-322. pmid: 8786130
[13]	Bellizzi JJ, Widom J, Kemp C, Lu JY, Das AK, Hofmann SL, Clardy J. The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis. Proc Natl Acad Sci USA, 2000, 97(9): 4573-4578. doi: 10.1073/pnas.080508097 pmid: 10781062
[14]	Harrison PJ. Alzheimer's disease and the beta amyloid gene. BMJ, 1991, 302(6791): 1478-1479. pmid: 1906764
[15]	Lyly A, von Schantz C, Salonen T, Kopra O, Saarela J, Jauhiainen M, Kyttälä A, Jalanko A. Glycosylation, transport, and complex formation of palmitoyl protein thioesterase 1 (PPT1)--distinct characteristics in neurons. BMC Cell Biol, 2007, 8: 22. pmid: 17565660
[16]	Wang R, Borazjani A, Matthews AT, Mangum LC, Edelmann MJ, Ross MK. Identification of palmitoyl protein thioesterase 1 in human THP1 monocytes and macrophages and characterization of unique biochemical activities for this enzyme. Biochemistry, 2013, 52(43): 7559-7574. doi: 10.1021/bi401138s pmid: 24083319
[17]	Yang CL, Wang XC. Lysosome biogenesis: Regulation and functions. J Cell Biol, 2021, 220(6): e202102001. doi: 10.1083/jcb.202102001
[18]	Yun HR, Jo YH, Kim J, Nguyen NNY, Shin Y, Kim SS, Choi TG. Palmitoyl protein thioesterase 1 is essential for myogenic autophagy of C2C12 skeletal myoblast. Front Physiol, 2020, 11: 569221. doi: 10.3389/fphys.2020.569221
[19]	Mondal A, Appu AP, Sadhukhan T, Bagh MB, Previde RM, Sadhukhan S, Stojilkovic S, Liu AY, Mukherjee AB. Ppt1-deficiency dysregulates lysosomal Ca(++) homeostasis contributing to pathogenesis in a mouse model of CLN1 disease. J Inherit Metab Dis, 2022, 45(3): 635-656. doi: 10.1002/jimd.v45.3
[20]	Kim SJ, Zhang ZJ, Hitomi E, Lee YC, Mukherjee AB. Endoplasmic reticulum stress-induced caspase-4 activation mediates apoptosis and neurodegeneration in INCL. Hum Mol Genet, 2006, 15(11): 1826-1834. doi: 10.1093/hmg/ddl105
[21]	Rebecca VW, Nicastri MC, Fennelly C, Chude CI, Barber-Rotenberg JS, Ronghe A, McAfee Q, McLaughlin NP, Zhang G, Goldman AR, Ojha R, Piao SF, Noguera- Ortega E, Martorella A, Alicea GM, Lee JJ, Schuchter LM, Xu XW, Herlyn M, Marmorstein R, Gimotty PA, Speicher DW, Winkler JD, Amaravadi RK. PPT1 promotes tumor growth and is the molecular target of chloroquine derivatives in cancer. Cancer Discov, 2019, 9(2): 220-229. doi: 10.1158/2159-8290.CD-18-0706 pmid: 30442709
[22]	Zhang ZJ, Lee YC, Kim SJ, Choi MS, Tsai PC, Xu Y, Xiao YJ, Zhang P, Heffer A, Mukherjee AB. Palmitoyl-protein thioesterase-1 deficiency mediates the activation of the unfolded protein response and neuronal apoptosis in INCL. Hum Mol Genet, 2006, 15(2): 337-346. pmid: 16368712
[23]	Goswami R, Ahmed M, Kilkus J, Han T, Dawson SA, Dawson G.Differential regulation of ceramide in lipid-rich microdomains (rafts): antagonistic role of palmitoyl:protein thioesterase and neutral sphingomyelinase 2. J Neurosci Res, 2005, 81(2): 208-217. pmid: 15929065
[24]	Danyukova T, Ariunbat K, Thelen M, Brocke- Ahmadinejad N, Mole SE, Storch S. Loss of CLN7 results in depletion of soluble lysosomal proteins and impaired mTOR reactivation. Hum Mol Genet, 2018, 27(10): 1711-1722. doi: 10.1093/hmg/ddy076 pmid: 29514215
[25]	Shyng C, Macauley SL, Dearborn JT, Sands MS.Widespread expression of a membrane-tethered version of the soluble lysosomal enzyme palmitoyl protein thioesterase-1. JIMD Rep, 2017, 36: 85-92. doi: 10.1007/8904_2017_1 pmid: 28213849
[26]	Granger E, McNee G, Allan V, Woodman P. The role of the cytoskeleton and molecular motors in endosomal dynamics. Semin Cell Dev Biol, 2014, 31(100): 20-29. doi: 10.1016/j.semcdb.2014.04.011
[27]	Sapir T, Segal M, Grigoryan G, Hansson KM, James P, Segal M, Reiner O. The interactome of palmitoyl-protein thioesterase 1 (PPT1) affects neuronal morphology and function. Front Cell Neurosci, 2019, 13: 92. doi: 10.3389/fncel.2019.00092 pmid: 30918483
[28]	Sarkar C, Sadhukhan T, Bagh MB, Appu AP, Chandra G, Mondal A, Saha A, Mukherjee AB. Cln1-mutations suppress Rab7-RILP interaction and impair autophagy contributing to neuropathology in a mouse model of infantile neuronal ceroid lipofuscinosis. J Inherit Metab Dis, 2020, 43(5): 1082-1101. doi: 10.1002/jimd.12242 pmid: 32279353
[29]	Chen YF, Chen YT, Chiu WT, Shen MR. Remodeling of calcium signaling in tumor progression. J Biomed Sci, 2013, 20(1): 23. doi: 10.1186/1423-0127-20-23
[30]	Saha A, Kim SJ, Zhang ZJ, Lee YC, Sarkar C, Tsai PC, Mukherjee AB. RAGE signaling contributes to neuroinflammation in infantile neuronal ceroid lipofuscinosis. FEBS Lett, 2008, 582(27): 3823-3831. doi: 10.1016/j.febslet.2008.10.015 pmid: 18948101
[31]	Ahtiainen L, Kolikova J, Mutka AL, Luiro K, Gentile M, Ikonen E, Khiroug L, Jalanko A, Kopra O. Palmitoyl protein thioesterase 1 (Ppt1)-deficient mouse neurons show alterations in cholesterol metabolism and calcium homeostasis prior to synaptic dysfunction. Neurobiol Dis, 2007, 28(1): 52-64. pmid: 17656100
[32]	Lloyd-Evans E, Platt FM. Lysosomal Ca(2+) homeostasis: role in pathogenesis of lysosomal storage diseases. Cell Calcium, 2011, 50(2): 200-205. doi: 10.1016/j.ceca.2011.03.010 pmid: 21724254
[33]	Brun S, Bestion E, Raymond E, Bassissi F, Jilkova ZM, Mezouar S, Rachid M, Novello M, Tracz J, Hamaï A, Lalmanach G, Vanderlynden L, Legouffe R, Stauber J, Schubert T, Plach MG, Courcambeck J, Drouot C, Jacquemot G, Serdjebi C, Roth G, Baudoin JP, Ansaldi C, Decaens T, Halfon P. GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinoma via modulation of lysosomal functions. Autophagy, 2022, 18(3): 678-694. doi: 10.1080/15548627.2021.1988357
[34]	Dietschy JM, Turley SD. Thematic review series: brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J Lipid Res, 2004, 45(8): 1375-1397. doi: 10.1194/jlr.R400004-JLR200 pmid: 15254070
[35]	Ahtiainen L, Luiro K, Kauppi M, Tyynelä J, Kopra O, Jalanko A. Palmitoyl protein thioesterase 1 (PPT1) deficiency causes endocytic defects connected to abnormal saposin processing. Exp Cell Res, 2006, 312(9): 1540-1553. pmid: 16542649
[36]	Mutka AL, Lusa S, Linder MD, Jokitalo E, Kopra O, Jauhiainen M, Ikonen E. Secretion of sterols and the NPC2 protein from primary astrocytes. J Biol Chem, 2004, 279(47): 48654-48662. doi: 10.1074/jbc.M405345200
[37]	Wei H, Zhang ZJ, Saha A, Peng SY, Chandra G, Quezado Z, Mukherjee AB. Disruption of adaptive energy metabolism and elevated ribosomal p-S6K1 levels contribute to INCL pathogenesis: partial rescue by resveratrol. Hum Mol Genet, 2011, 20(6): 1111-1121. doi: 10.1093/hmg/ddq555 pmid: 21224254
[38]	Woloszynek JC, Coleman T, Semenkovich CF, Sands MS. Lysosomal dysfunction results in altered energy balance. J Biol Chem, 2007, 282(49): 35765-35771. doi: 10.1074/jbc.M705124200 pmid: 17911106
[39]	Khaibullina A, Kenyon N, Guptill V, Quezado MM, Wang L, Koziol D, Wesley R, Moya PR, Zhang ZJ, Saha A, Mukherjee AB, Quezado ZMN. In a model of Batten disease, palmitoyl protein thioesterase-1 deficiency is associated with brown adipose tissue and thermoregulation abnormalities. PLoS One, 2012, 7(11): e48733. doi: 10.1371/journal.pone.0048733
[40]	Santavuori P, Haltia M, Rapola J. Infantile type of so-called neuronal ceroid-lipofuscinosis. Dev Med Child Neurol, 1974, 16(5): 644-653. doi: 10.1111/j.1469-8749.1974.tb04183.x pmid: 4371326
[41]	Mumby SM. Reversible palmitoylation of signaling proteins. Curr Opin Cell Biol, 1997, 9(2): 148-154. pmid: 9069258
[42]	Lyly A, Marjavaara SK, Kyttälä A, Uusi-Rauva K, Luiro K, Kopra O, Martinez LO, Tanhuanpää K, Kalkkinen N, Suomalainen A, Jauhiainen M, Jalanko A. Deficiency of the INCL protein Ppt1 results in changes in ectopic F1-ATP synthase and altered cholesterol metabolism. Hum Mol Genet, 2008, 17(10): 1406-1417. doi: 10.1093/hmg/ddn028 pmid: 18245779
[43]	Zhao WZ, Su J, Wang YT, Qian TJ, Liu Y. Functional importance of palmitoyl protein thioesterase 1 (PPT1) expression by Sertoli cells in mediating cholesterol metabolism and maintenance of sperm quality. Mol Reprod Dev, 2019, 86(8): 984-998. doi: 10.1002/mrd.23173 pmid: 31134714
[44]	Chojnacka K, Zarzycka M, Mruk DD. Biology of the sertoli cell in the fetal, pubertal, and adult mammalian testis. Results Probl Cell Differ, 2016, 58: 225-251. doi: 10.1007/978-3-319-31973-5_9 pmid: 27300181
[45]	Annunziata I, Sano R, d'Azzo A. Mitochondria-associated ER membranes (MAMs) and lysosomal storage diseases. Cell Death Dis, 2018, 9(3): 328. doi: 10.1038/s41419-017-0025-4 pmid: 29491402
[46]	Balouch B, Nagorsky H, Pham T, LaGraff JT, Chu-LaGraff Q. Human INCL fibroblasts display abnormal mitochondrial and lysosomal networks and heightened susceptibility to ROS-induced cell death. PLoS One, 2021, 16(2): e0239689. doi: 10.1371/journal.pone.0239689
[47]	Hickey AJ, Chotkowski HL, Singh N, Ault JG, Korey CA, MacDonald ME, Glaser RL. Palmitoyl-protein thioesterase1 deficiency in Drosophila melanogaster causes accumulation of abnormal storage material and reduced life span. Genetics, 2006, 172(4): 2379-2390. doi: 10.1534/genetics.105.053306
[48]	Pezzini F, Gismondi F, Tessa A, Tonin P, Carrozzo R, Mole SE, Santorelli FM, Simonati A. Involvement of the mitochondrial compartment in human NCL fibroblasts. Biochem Biophys Res Commun, 2011, 416(1-2): 159-164. doi: 10.1016/j.bbrc.2011.11.016
[49]	Meyer M, Kovács AD, Pearce DA. Decreased sensitivity of palmitoyl protein thioesterase 1-deficient neurons to chemical anoxia. Metab Brain Dis, 2017, 32(1): 275-279. doi: 10.1007/s11011-016-9919-6 pmid: 27722792
[50]	Bible E, Gupta P, Hofmann SL, Cooper JD. Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis. Neurobiol Dis, 2004, 16(2): 346-359. pmid: 15193291
[51]	Zhang XS, Wang MT, Feng BY, Zhang QY, Tong J, Wang MY, Lu CB, Peng SY. Seizures in PPT1 knock-in mice are associated with inflammatory activation of microglia. Int J Mol Sci, 2022, 23(10): 5586. doi: 10.3390/ijms23105586
[52]	Chandra G, Bagh MB, Peng SY, Saha A, Sarkar C, Moralle M, Zhang ZJ, Mukherjee AB. Cln1 gene disruption in mice reveals a common pathogenic link between two of the most lethal childhood neurodegenerative lysosomal storage disorders. Hum Mol Genet, 2015, 24(19): 5416-5432. doi: 10.1093/hmg/ddv266 pmid: 26160911
[53]	Lange J, Haslett LJ, Lloyd-Evans E, Pocock JM, Sands MS, Williams BP, Cooper JD. Compromised astrocyte function and survival negatively impact neurons in infantile neuronal ceroid lipofuscinosis. Acta Neuropathol Commun, 2018, 6(1): 74. doi: 10.1186/s40478-018-0575-4
[54]	Chu-LaGraff Q, Blanchette C, O'Hern P, Denefrio C. The Batten disease Palmitoyl Protein Thioesterase 1 gene regulates neural specification and axon connectivity during Drosophila embryonic development. PLoS One, 2010, 5(12): e14402. doi: 10.1371/journal.pone.0014402
[55]	Koster KP, Francesconi W, Berton F, Alahmadi S, Srinivas R, Yoshii A. Developmental NMDA receptor dysregulation in the infantile neuronal ceroid lipofuscinosis mouse model. eLife, 2019, 8: e40316. doi: 10.7554/eLife.40316
[56]	Kielar C, Wishart TM, Palmer A, Dihanich S, Wong AM, Macauley SL, Chan CH, Sands MS, Pearce DA, Cooper JD, Gillingwater TH. Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Hum Mol Genet, 2009, 18(21): 4066-4080. doi: 10.1093/hmg/ddp355 pmid: 19640925
[57]	Wishart TM, Paterson JM, Short DM, Meredith S, Robertson KA, Sutherland C, Cousin MA, Dutia MB, Gillingwater TH. Differential proteomics analysis of synaptic proteins identifies potential cellular targets and protein mediators of synaptic neuroprotection conferred by the slow Wallerian degeneration (Wlds) gene. Mol Cell Proteomics, 2007, 6(8): 1318-1330. doi: 10.1074/mcp.M600457-MCP200 pmid: 17470424
[58]	Virmani T, Gupta P, Liu XR, Kavalali ET, Hofmann SL. Progressively reduced synaptic vesicle pool size in cultured neurons derived from neuronal ceroid lipofuscinosis-1 knockout mice. Neurobiol Dis, 2005, 20(2): 314-323. pmid: 16242638
[59]	Brady S, Morfini G. A perspective on neuronal cell death signaling and neurodegeneration. Mol Neurobiol, 2010, 42(1): 25-31. doi: 10.1007/s12035-010-8128-2 pmid: 20480262
[60]	Kanaan NM, Pigino GF, Brady ST, Lazarov O, Binder LI, Morfini GA. Axonal degeneration in Alzheimer's disease: when signaling abnormalities meet the axonal transport system. Exp Neurol, 2013, 246: 44-53. doi: 10.1016/j.expneurol.2012.06.003 pmid: 22721767
[61]	Ryan M, Graham LA, Stevens TH. Voa1p functions in V-ATPase assembly in the yeast endoplasmic reticulum. Mol Biol Cell, 2008, 19(12): 5131-5142. doi: 10.1091/mbc.E08-06-0629 pmid: 18799613
[62]	Bagh MB, Peng SY, Chandra G, Zhang ZJ, Singh SP, Pattabiraman N, Liu AY, Mukherjee AB. Misrouting of v-ATPase subunit V0a1 dysregulates lysosomal acidification in a neurodegenerative lysosomal storage disease model. Nat Commun, 2017, 8: 14612. doi: 10.1038/ncomms14612 pmid: 28266544
[63]	Appu AP, Bagh MB, Sadhukhan T, Mondal A, Casey S, Mukherjee AB. Cln3-mutations underlying juvenile neuronal ceroid lipofuscinosis cause significantly reduced levels of Palmitoyl-protein thioesterases-1 (Ppt1)-protein and Ppt1-enzyme activity in the lysosome. J Inherit Metab Dis, 2019, 42(5): 944-954. doi: 10.1002/jimd.12106 pmid: 31025705
[64]	Yuan W, Lu LX, Rao MD, Huang Y, Liu CE, Liu S, Zhao Y, Liu HC, Zhu JL, Chao TZ, Wu C, Ren JY, Lv LX, Li WQ, Qi SQ, Liang YM, Yue SJ, Gao J, Zhang ZJ, Kong EY. GFAP hyperpalmitoylation exacerbates astrogliosis and neurodegenerative pathology in PPT1-deficient mice. Proc Natl Acad Sci USA, 2021, 118(13): e2022261118. doi: 10.1073/pnas.2022261118
[65]	Zhou BH, Hao QY, Liang YM, Kong EY. Protein palmitoylation in cancer: molecular functions and therapeutic potential. Mol Oncol, 2023, 17(1): 3-26. doi: 10.1002/mol2.v17.1
[66]	Wei H, Kim SJ, Zhang ZJ, Tsai PC, Wisniewski KE, Mukherjee AB. ER and oxidative stresses are common mediators of apoptosis in both neurodegenerative and non-neurodegenerative lysosomal storage disorders and are alleviated by chemical chaperones. Hum Mol Genet, 2008, 17(4): 469-477. doi: 10.1093/hmg/ddm324 pmid: 17989065
[67]	Macauley SL, Wong AMS, Shyng C, Augner DP, Dearborn JT, Pearse Y, Roberts MS, Fowler SC, Cooper JD, Watterson DM, Sands MS. An anti-neuroinflammatory that targets dysregulated glia enhances the efficacy of CNS-directed gene therapy in murine infantile neuronal ceroid lipofuscinosis. J Neurosci, 2014, 34(39): 13077-13082. doi: 10.1523/JNEUROSCI.2518-14.2014 pmid: 25253854
[68]	Kim SJ, Zhang ZJ, Lee YC, Mukherjee AB. Palmitoyl- protein thioesterase-1 deficiency leads to the activation of caspase-9 and contributes to rapid neurodegeneration in INCL. Hum Mol Genet, 2006, 15(10): 1580-1586. doi: 10.1093/hmg/ddl078
[69]	Cooper JD, Messer A, Feng AK, Chua-Couzens J, Mobley WC. Apparent loss and hypertrophy of interneurons in a mouse model of neuronal ceroid lipofuscinosis: evidence for partial response to insulin-like growth factor-1 treatment. J Neurosci, 1999, 19(7): 2556-2567. pmid: 10087069
[70]	Oswald MJ, Palmer DN, Kay GW, Shemilt SJA, Rezaie P, Cooper JD. Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6). Neurobiol Dis, 2005, 20(1): 49-63. pmid: 16137566
[71]	Cooper JD. Moving towards therapies for juvenile Batten disease?. Exp Neurol, 2008, 211(2): 329-331. doi: 10.1016/j.expneurol.2008.02.016 pmid: 18400221
[72]	Pontikis CC, Cella CV, Parihar N, Lim MJ, Chakrabarti S, Mitchison HM, Mobley WC, Rezaie P, Pearce DA, Cooper JD. Late onset neurodegeneration in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation. Brain Res, 2004, 1023(2): 231-242. pmid: 15374749
[73]	Tyynelä J, Cooper JD, Khan MN, Shemilts SJA, Haltia M. Hippocampal pathology in the human neuronal ceroid-lipofuscinoses: distinct patterns of storage deposition, neurodegeneration and glial activation. Brain Pathol, 2004, 14(4): 349-357. doi: 10.1111/j.1750-3639.2004.tb00077.x pmid: 15605981
[74]	Kielar C, Maddox L, Bible E, Pontikis CC, Macauley SL, Griffey MA, Wong M, Sands MS, Cooper JD. Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis. Neurobiol Dis, 2007, 25(1): 150-162. pmid: 17046272
[75]	Rebecca VW, Nicastri MC, McLaughlin N, Fennelly C, McAfee Q, Ronghe A, Nofal M, Lim CY, Witze E, Chude CI, Zhang G, Alicea GM, Piao SF, Murugan S, Ojha R, Levi SM, Wei Z, Barber-Rotenberg JS, Murphy ME, Mills GB, Lu YL, Rabinowitz J, Marmorstein R, Liu Q, Liu SJ, Xu XW, Herlyn M, Zoncu R, Brady DC, Speicher DW, Winkler JD, Amaravadi RK.A unified approach to targeting the lysosome's degradative and growth signaling roles. Cancer Discov, 2017, 7(11): 1266-1283.
[76]	Luo QQ, Li XY, Gan GF, Yang M, Chen X, Chen FX. PPT1 reduction contributes to erianin-induced growth inhibition in oral squamous carcinoma cells. Front Cell Dev Biol, 2021, 9: 764263. doi: 10.3389/fcell.2021.764263
[77]	Tian W, Li CY, Ren JQ, Li PF, Zhao JY, Li S, Dong DS. Identification of PPT1 as a lysosomal core gene with prognostic value in hepatocellular carcinoma. Biosci Rep, 2023, 43(5): BSR20230067. doi: 10.1042/BSR20230067
[78]	Xu JJ, Su Z, Cheng X, Hu SB, Wang WJ, Zou TH, Zhou X, Song ZF, Xia Y, Gao Y, Zheng QC. High PPT1 expression predicts poor clinical outcome and PPT1 inhibitor DC661 enhances sorafenib sensitivity in hepatocellular carcinoma. Cancer Cell Int, 2022, 22(1): 115. doi: 10.1186/s12935-022-02508-y pmid: 35277179
[79]	Weng JL, Liu SQ, Zhou Q, Xu WX, Xu MH, Gao DM, Shen YH, Yi Y, Shi Y, Dong QZ, Zhou CH, Ren N. Intratumoral PPT1-positive macrophages determine immunosuppressive contexture and immunotherapy response in hepatocellular carcinoma. J Immunother Cancer, 2023, 11(6): e006655. doi: 10.1136/jitc-2022-006655
[80]	Yang JB, Zeng LT, Chen RW, Zheng SY, Zhou Y, Chen RF. Characterization of heterogeneous metabolism in hepatocellular carcinoma identifies new therapeutic target and treatment strategy. Front Immunol, 2023, 14: 1076587. doi: 10.3389/fimmu.2023.1076587
[81]	Cho S, Dawson G. Palmitoyl protein thioesterase 1 protects against apoptosis mediated by Ras-Akt-caspase pathway in neuroblastoma cells. J Neurochem, 2000, 74(4): 1478-1488. doi: 10.1046/j.1471-4159.2000.0741478.x pmid: 10737604
[82]	Cho S, Dawson PE, Dawson G. Antisense palmitoyl protein thioesterase 1 (PPT1) treatment inhibits PPT1 activity and increases cell death in LA-N-5 neuroblastoma cells. J Neurosci Res, 2000, 62(2): 234-240. pmid: 11020216
[83]	Phadatare P, Debnath J. Lysosomal lipid peroxidation mediates immunogenic cell death. J Clin Invest, 2023, 133(8): e169240. doi: 10.1172/JCI169240
[84]	Zhou BH, Wang Y, Zhang LC, Shi XY, Kong HS, Zhang MJ, Liu Y, Shao X, Liu ZL, Song HX, Li WS, Gao XX, Chang YL, Dou CZ, Guo WZ, Zhang SJ, Kang XH, Gao J, Liang YM, Zheng JF, Kong EY. The palmitoylation of AEG-1 dynamically modulates the progression of hepatocellular carcinoma. Theranostics, 2022, 12(16): 6898-6914. doi: 10.7150/thno.78377 pmid: 36276642
[85]	Vergoten G, Bailly C. Binding of hydroxychloroquine and chloroquine dimers to palmitoyl-protein thioesterase 1 (PPT1) and its glycosylated forms: a computational approach. J Biomol Struct Dyn, 2022, 40(18): 8197-8205. doi: 10.1080/07391102.2021.1908167
[86]	Duarte D, Vale N. How antimalarials and antineoplastic drugs can interact in combination therapies: a perspective on the role of PPT1 enzyme. Curr Drug Metab, 2021, 22(13): 1009-1016. doi: 10.2174/1389200222666211118114057 pmid: 34791996
[87]	Lu JY, Nelvagal HR, Wang LL, Birnbaum SG, Cooper JD, Hofmann SL. Intrathecal enzyme replacement therapy improves motor function and survival in a preclinical mouse model of infantile neuronal ceroid lipofuscinosis. Mol Genet Metab, 2015, 116(1-2): 98-105. doi: 10.1016/j.ymgme.2015.05.005
[88]	Meng L, Sin N, Crews CM. The antiproliferative agent didemnin B uncompetitively inhibits palmitoyl protein thioesterase. Biochemistry, 1998, 37(29): 10488-10492. pmid: 9671519
[89]	Roberts MS, Macauley SL, Wong AM, Yilmas D, Hohm S, Cooper JD, Sands MS. Combination small molecule PPT1 mimetic and CNS-directed gene therapy as a treatment for infantile neuronal ceroid lipofuscinosis. J Inherit Metab Dis, 2012, 35(5): 847-857. doi: 10.1007/s10545-011-9446-x pmid: 22310926
[90]	Harding JJ, Awada A, Roth G, Decaens T, Merle P, Kotecki N, Dreyer C, Ansaldi C, Rachid M, Mezouar S, Menut A, Bestion EN, Paradis V, Halfon P, Abou-Alfa GK, Raymond E. First-in-human effects of ppt1 inhibition using the oral treatment with GNS561/Ezurpimtrostat in patients with primary and secondary liver cancers. Liver Cancer, 2022, 11(3): 268-77. doi: 10.1159/000522418 pmid: 35949290
[91]	Saha A, Sarkar C, Singh SP, Zhang ZJ, Munasinghe J, Peng SY, Chandra G, Kong EY, Mukherjee AB. The blood-brain barrier is disrupted in a mouse model of infantile neuronal ceroid lipofuscinosis: amelioration by resveratrol. Hum Mol Genet, 2012, 21(10): 2233-2244. doi: 10.1093/hmg/dds038 pmid: 22331300
[92]	Zhang Z, Butler JD, Levin SW, Wisniewski KE, Brooks SS, Mukherjee AB. Lysosomal ceroid depletion by drugs: therapeutic implications for a hereditary neurodegenerative disease of childhood. Nat Med, 2001, 7(4): 478-484. pmid: 11283676
[93]	Nelvagal HR, Eaton SL, Wang SH, Eultgen EM, Takahashi K, Le SQ, Nesbitt R, Dearborn JT, Siano N, Puhl AC, Dickson PI, Thompson G, Murdoch F, Brennan PM, Gray M, Greenhalgh SN, Tennant P, Gregson R, Clutton E, Nixon J, Proudfoot C, Guido S, Lillico SG, Whitelaw CBA, Lu JY, Hofmann SL, Ekins S, Sands MS, Wishart TM, Cooper JD. Cross-species efficacy of enzyme replacement therapy for CLN1 disease in mice and sheep. J Clin Invest, 2022, 132(20): e163107. doi: 10.1172/JCI163107
[94]	Hofmann SL, Das AK, Lu JY, Soyombo AA.Positional candidate gene cloning of CLN1. Adv Genet, 2001, 45: 69-92. pmid: 11332777
[95]	Hawkes C, Kar S. The insulin-like growth factor-II/ mannose-6-phosphate receptor: structure, distribution and function in the central nervous system. Brain Res Brain Res Rev, 2004, 44(2-3): 117-140. doi: 10.1016/j.brainresrev.2003.11.002
[96]	Lu JY, Hu J, Hofmann SL. Human recombinant palmitoyl-protein thioesterase-1 (PPT1) for preclinical evaluation of enzyme replacement therapy for infantile neuronal ceroid lipofuscinosis. Mol Genet Metab, 2010, 99(4): 374-378. doi: 10.1016/j.ymgme.2009.12.002
[97]	Tamaki SJ, Jacobs Y, Dohse M, Capela A, Cooper JD, Reitsma M, He DP, Tushinski R, Belichenko PV, Salehi A, Mobley W, Gage FH, Huhn S, Tsukamoto AS, Weissman IL, Uchida N. Neuroprotection of host cells by human central nervous system stem cells in a mouse model of infantile neuronal ceroid lipofuscinosis. Cell Stem Cell, 2009, 5(3): 310-319. doi: 10.1016/j.stem.2009.05.022 pmid: 19733542
[98]	Fukata Y, Fukata M. Protein palmitoylation in neuronal development and synaptic plasticity. Nat Rev Neurosci, 2010, 11(3): 161-175. doi: 10.1038/nrn2788 pmid: 20168314
[99]	Huang K, El-Husseini A. Modulation of neuronal protein trafficking and function by palmitoylation. Curr Opin Neurobiol, 2005, 15(5): 527-535. pmid: 16125924
[100]	Ko PJ, Dixon SJ. Protein palmitoylation and cancer. EMBO Rep, 2018, 19(10): e46666. doi: 10.15252/embr.201846666

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

溶酶体酶PPT1介导的细胞稳态调控及疾病发生的研究进展

Progress on lysosomal PPT1-mediated regulation of cellular homeostasis and pathogenesis

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 4

参考文献 100

相关文章 4

编辑推荐

Metrics

药物	作用	参考文献
Didemnin B	对PPT1具有非竞争性抑制作用	[88]
AAV (adeno-associated virus type，重组腺相关病毒)	AAV介导的基因治疗可显著改善PPT1缺陷小鼠的生化、组织学和行为	[89]
GNS561/Ezurpimtrostat	通过与PPT1相互作用，抑制晚期自噬和扩大溶酶体的剂量依赖性积聚，阻止癌细胞增殖	[90]
RSV(白藜芦醇)	可显着降低T_H17细胞、IL-17A和MMP的水平，并提高紧密连接蛋白的水平，从而提高BBB(血脑屏障)完整性	[91]
Cysteamine、N-acetylcysteine	通过抑制半胱氨酸硫酯的形成和阻断蜡样积累来发挥作用，从而减少储存物质的积累	[92]

[1]	刘莉莉, 郭爱伟, 李青青, 吴培福, 杨亚晋, 陈粉粉, 李素华, 郭盘江, 张勤. 泛素化途径在奶牛乳脂生成过程中的调控作用[J]. 遗传, 2020, 42(6): 548-555.
[2]	郝振华, 李巍. Muted蛋白介导CD63在嗜铬细胞大致密核粒的定位[J]. 遗传, 2016, 38(8): 718-723.
[3]	李金环, 寿佳, 吴强. CRISPR/Cas9系统在基因组DNA片段编辑中的应用[J]. 遗传, 2015, 37(10): 992-291.
[4]	张喆，李巍. Weibel-Palade小体形成和功能研究进展[J]. 遗传, 2009, 31(9): 882-888.