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Bioprocess 2024
自噬作为多种疾病治疗的靶点
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Abstract:
自噬是一种溶酶体降解途径，可降解错误折叠的蛋白质、清除不必要或损伤的细胞器并消除感染的病毒或细菌等病原体，从而维持真核细胞的稳态。自噬对于细胞生存、生物能稳态、机体发育至关重要，与许多人类疾病的发生发展密切相关。本综述总结了自噬在癌症和神经退行性疾病中作用的研究进展，并讨论了靶向自噬的潜在疾病治疗方法。
Autophagy is a lysosomal degradation pathway, which degrades misfolded proteins, removes unnecessary or damaged organelles and eliminates intracellular pathogens, such as viruses and bacteria, to maintain cellular homeostasis. Autophagy is critical for cell survival, bioenergetic homeostasis and organismal development, and is closely associated with many human diseases. This review summarizes current advances in the role of autophagy in cancer and neurodegenerative diseases, and discusses potential therapeutic approaches to target autophagy.
| [1] | Parada, C.A., De Oliveira, I.P., Gewehr, M.C.F., Machado-Neto, J.A., Lima, K., Eichler, R.A.S., et al. (2022) Effect of FKBP12-Derived Intracellular Peptides on Rapamycin-Induced FKBP-FRB Interaction and Autophagy. Cells, 11, Article 385. https://doi.org/10.3390/cells11030385 |
| [2] | Dikic, I. and Elazar, Z. (2018) Mechanism and Medical Implications of Mammalian Autophagy. Nature Reviews Molecular Cell Biology, 19, 349-364. https://doi.org/10.1038/s41580-018-0003-4 |
| [3] | Lopes, V.R., Loitto, V., Audinot, J., Bayat, N., Gutleb, A.C. and Cristobal, S. (2016) Dose-Dependent Autophagic Effect of Titanium Dioxide Nanoparticles in Human Hacat Cells at Non-Cytotoxic Levels. Journal of Nanobiotechnology, 14, Article No. 22. https://doi.org/10.1186/s12951-016-0174-0 |
| [4] | Wang, N., Wei, L., Liu, D., Zhang, Q., Xia, X., Ding, L., et al. (2022) Identification and Validation of Autophagy-Related Genes in Diabetic Retinopathy. Frontiers in Endocrinology, 13, Article 867600. https://doi.org/10.3389/fendo.2022.867600 |
| [5] | Levine, B. and Kroemer, G. (2008) Autophagy in the Pathogenesis of Disease. Cell, 132, 27-42. https://doi.org/10.1016/j.cell.2007.12.018 |
| [6] | Rabinowitz, J.D. and White, E. (2010) Autophagy and Metabolism. Science, 330, 1344-1348. https://doi.org/10.1126/science.1193497 |
| [7] | Klionsky, D.J. (2007) Autophagy: From Phenomenology to Molecular Understanding in Less than a Decade. Nature Reviews Molecular Cell Biology, 8, 931-937. https://doi.org/10.1038/nrm2245 |
| [8] | Nakatogawa, H., Suzuki, K., Kamada, Y. and Ohsumi, Y. (2009) Dynamics and Diversity in Autophagy Mechanisms: Lessons from Yeast. Nature Reviews Molecular Cell Biology, 10, 458-467. https://doi.org/10.1038/nrm2708 |
| [9] | Li, X., He, S. and Ma, B. (2020) Autophagy and Autophagy-Related Proteins in Cancer. Molecular Cancer, 19, Article No. 12 https://doi.org/10.1186/s12943-020-1138-4 |
| [10] | Mizushima, N. (2007) Autophagy: Process and Function. Genes & Development, 21, 2861-2873. https://doi.org/10.1101/gad.1599207 |
| [11] | Ichimura, Y., Kirisako, T., Takao, T., Satomi, Y., Shimonishi, Y., Ishihara, N., et al. (2000) A Ubiquitin-Like System Mediates Protein Lipidation. Nature, 408, 488-492. https://doi.org/10.1038/35044114 |
| [12] | Hamasaki, M., Furuta, N., Matsuda, A., Nezu, A., Yamamoto, A., Fujita, N., et al. (2013) Autophagosomes Form at ER-Mitochondria Contact Sites. Nature, 495, 389-393. https://doi.org/10.1038/nature11910 |
| [13] | Rogov, V., D？tsch, V., Johansen, T. and Kirkin, V. (2014) Interactions between Autophagy Receptors and Ubiquitin-Like Proteins Form the Molecular Basis for Selective Autophagy. Molecular Cell, 53, 167-178. https://doi.org/10.1016/j.molcel.2013.12.014 |
| [14] | Lu, K., Psakhye, I. and Jentsch, S. (2014) Autophagic Clearance of PolyQ Proteins Mediated by Ubiquitin-Atg8 Adaptors of the Conserved CUET Protein Family. Cell, 158, 549-563. https://doi.org/10.1016/j.cell.2014.05.048 |
| [15] | White, E. and DiPaola, R.S. (2009) The Double-Edged Sword of Autophagy Modulation in Cancer. Clinical Cancer Research, 15, 5308-5316. https://doi.org/10.1158/1078-0432.ccr-07-5023 |
| [16] | Jin, S. and White, E. (2007) Role of Autophagy in Cancer: Management of Metabolic Stress. Autophagy, 3, 28-31. https://doi.org/10.4161/auto.3269 |
| [17] | White, E. (2012) Deconvoluting the Context-Dependent Role for Autophagy in Cancer. Nature Reviews Cancer, 12, 401-410. https://doi.org/10.1038/nrc3262 |
| [18] | Galluzzi, L., Pietrocola, F., Bravo-San Pedro, J.M., Amaravadi, R.K., Baehrecke, E.H., Cecconi, F., et al. (2015) Autophagy in Malignant Transformation and Cancer Progression. The EMBO Journal, 34, 856-880. https://doi.org/10.15252/embj.201490784 |
| [19] | Li, Z., Chen, B., Wu, Y., Jin, F., Xia, Y. and Liu, X. (2010) Genetic and Epigenetic Silencing of the Beclin 1 Gene in Sporadic Breast Tumors. BMC Cancer, 10, Article No. 98. https://doi.org/10.1186/1471-2407-10-98 |
| [20] | Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., et al. (2003) Promotion of Tumorigenesis by Heterozygous Disruption of the Beclin 1 Autophagy Gene. Journal of Clinical Investigation, 112, 1809-1820. https://doi.org/10.1172/jci20039 |
| [21] | Kang, M.R., Kim, M.S., Oh, J.E., Kim, Y.R., Song, S.Y., Kim, S.S., et al. (2009) Frameshift Mutations of Autophag Related Genes ATG2B, ATG5, ATG9B and ATG12 in Gastric and Colorectal Cancers with Microsatellite Instability. The Journal of Pathology, 217, 702-706. https://doi.org/10.1002/path.2509 |
| [22] | Wible, D.J., Chao, H., Tang, D.G. and Bratton, S.B. (2019) ATG5 Cancer Mutations and Alternative mRNA Splicing Reveal a Conjugation Switch That Regulates ATG12-ATG5-ATG16L1 Complex Assembly and Autophagy. Cell Discovery, 5, Article No. 42. https://doi.org/10.1038/s41421-019-0110-1 |
| [23] | Tsukamoto, S., Kuma, A., Murakami, M., Kishi, C., Yamamoto, A. and Mizushima, N. (2008) Autophagy Is Essential for Preimplantation Development of Mouse Embryos. Science, 321, 117-120. https://doi.org/10.1126/science.1154822 |
| [24] | Kocaturk, N.M., Akkoc, Y., Kig, C., Bayraktar, O., Gozuacik, D. and Kutlu, O. (2019) Autophagy as a Molecular Target for Cancer Treatment. European Journal of Pharmaceutical Sciences, 134, 116-137. https://doi.org/10.1016/j.ejps.2019.04.011 |
| [25] | Wei, H., Wei, S., Gan, B., Peng, X., Zou, W. and Guan, J. (2011) Suppression of Autophagy by FIP200 Deletion Inhibits Mammary Tumorigenesis. Genes & Development, 25, 1510-1527. https://doi.org/10.1101/gad.2051011 |
| [26] | Gong, C., Bauvy, C., Tonelli, G., Yue, W., Deloménie, C., Nicolas, V., et al. (2012) Beclin 1 and Autophagy Are Required for the Tumorigenicity of Breast Cancer Stem-Like/Progenitor Cells. Oncogene, 32, 2261-2272. https://doi.org/10.1038/onc.2012.252 |
| [27] | Yue, W., Hama？, A., Tonelli, G., Bauvy, C., Nicolas, V., Tharinger, H., et al. (2013) Inhibition of the Autophagic Flux by Salinomycin in Breast Cancer Stem-Like/Progenitor Cells Interferes with Their Maintenance. Autophagy, 9, 714-729. https://doi.org/10.4161/auto.23997 |
| [28] | Jin, M., Liu, X., Wu, Y., Lou, Y., Li, X. and Huang, G. (2022) Circular RNA EPB41 Expression Predicts Unfavorable Prognoses in NSCLC by Regulating mIR-486-3p/eIF5A Axis-Mediated Stemness. Cancer Cell International, 22, Article No. 219. https://doi.org/10.1186/s12935-022-02618-7 |
| [29] | Boya, P., Codogno, P. and Rodriguez-Muela, N. (2018) Autophagy in Stem Cells: Repair, Remodelling and Metabolic Reprogramming. Development, 145, dev146506. https://doi.org/10.1242/dev.146506 |
| [30] | Auberger, P. and Puissant, A. (2017) Autophagy, a Key Mechanism of Oncogenesis and Resistance in Leukemia. Blood, 129, 547-552. https://doi.org/10.1182/blood-2016-07-692707 |
| [31] | Bortnik, S. and Gorski, S.M. (2017) Clinical Applications of Autophagy Proteins in Cancer: from Potential Targets to Biomarkers. International Journal of Molecular Sciences, 18, Article 1496. https://doi.org/10.3390/ijms18071496 |
| [32] | Mo, S., Dai, W., Xiang, W., Li, Y., Feng, Y., Zhang, L., et al. (2019) Prognostic and Predictive Value of an Autophagy-Related Signature for Early Relapse in Stages I-III Colon Cancer. Carcinogenesis, 40, 861-870. https://doi.org/10.1093/carcin/bgz031 |
| [33] | Kimmelman, A.C. and White, E. (2017) Autophagy and Tumor Metabolism. Cell Metabolism, 25, 1037-1043. https://doi.org/10.1016/j.cmet.2017.04.004 |
| [34] | Katheder, N.S., Khezri, R., O’Farrell, F., Schultz, S.W., Jain, A., Rahman, M.M., et al. (2017) Microenvironmental Autophagy Promotes Tumour Growth. Nature, 541, 417-420. https://doi.org/10.1038/nature20815 |
| [35] | Katheder, N.S. and Rusten, T.E. (2017) Microenvironment and Tumors—A Nurturing Relationship. Autophagy, 13, 1241-1243. https://doi.org/10.1080/15548627.2017.1310361 |
| [36] | Shen, Z., Qin, L., Xu, T., Xia, L., Wang, X., Zhang, X., et al. (2016) Chloroquine Enhances the Efficacy of Cisplatin by Suppressing Autophagy in Human Adrenocortical Carcinoma Treatment. Drug Design, Development and Therapy, 10, 1035-1045. https://doi.org/10.2147/dddt.s101701 |
| [37] | Gong, C., Hu, C., Gu, F., Xia, Q., Yao, C., Zhang, L., et al. (2017) Co-Delivery of Autophagy Inhibitor ATG7 siRNA and Docetaxel for Breast Cancer Treatment. Journal of Controlled Release, 266, 272-286. https://doi.org/10.1016/j.jconrel.2017.09.042 |
| [38] | Eng, C.H., Wang, Z., Tkach, D., Toral-Barza, L., Ugwonali, S., Liu, S., et al. (2015) Macroautophagy Is Dispensable for Growth of KRAS Mutant Tumors and Chloroquine Efficacy. Proceedings of the National Academy of Sciences, 113, 182-187. https://doi.org/10.1073/pnas.1515617113 |
| [39] | Karsli-Uzunbas, G., Guo, J.Y., Price, S., Teng, X., Laddha, S.V., Khor, S., et al. (2014) Autophagy Is Required for Glucose Homeostasis and Lung Tumor Maintenance. Cancer Discovery, 4, 914-927. https://doi.org/10.1158/2159-8290.cd-14-0363 |
| [40] | Napolitano, G., Johnson, J.L., He, J., Rocca, C.J., Monfregola, J., Pestonjamasp, K., et al. (2015) Impairment of Chaperone-Mediated Autophagy Leads to Selective Lysosomal Degradation Defects in the Lysosomal Storage Disease Cystinosis. EMBO Molecular Medicine, 7, 158-174. https://doi.org/10.15252/emmm.201404223 |
| [41] | Degenhardt, K., Mathew, R., Beaudoin, B., Bray, K., Anderson, D., Chen, G., et al. (2006) Autophagy Promotes Tumor Cell Survival and Restricts Necrosis, Inflammation, and Tumorigenesis. Cancer Cell, 10, 51-64. https://doi.org/10.1016/j.ccr.2006.06.001 |
| [42] | Choi, A.M.K., Ryter, S.W. and Levine, B. (2013) Autophagy in Human Health and Disease. New England Journal of Medicine, 368, 651-662. https://doi.org/10.1056/nejmra1205406 |
| [43] | Li, Y., Huang, J., Pang, S., Wang, H., Zhang, A., Hawley, R.G., et al. (2017) Novel and Functional ATG12 Gene Variants in Sporadic Parkinson’s Disease. Neuroscience Letters, 643, 22-26. https://doi.org/10.1016/j.neulet.2017.02.028 |
| [44] | Friedman, L.G., Lachenmayer, M.L., Wang, J., He, L., Poulose, S.M., Komatsu, M., et al. (2012) Disrupted Autophagy Leads to Dopaminergic Axon and Dendrite Degeneration and Promotes Presynaptic Accumulation of α-Synuclein and LRRK2 in the Brain. The Journal of Neuroscience, 32, 7585-7593. https://doi.org/10.1523/jneurosci.5809-11.2012 |
| [45] | Sliter, D.A., Martinez, J., Hao, L., Chen, X., Sun, N., Fischer, T.D., et al. (2018) Parkin and Pink1 Mitigate Sting-Induced Inflammation. Nature, 561, 258-262. https://doi.org/10.1038/s41586-018-0448-9 |
| [46] | Huang, J. and Klionsky, D.J. (2007) Autophagy and Human Disease. Cell Cycle, 6, 1837-1849. https://doi.org/10.4161/cc.6.15.4511 |
| [47] | Wang, Y., Martinez-Vicente, M., Krüger, U., Kaushik, S., Wong, E., Mandelkow, E., et al. (2010) Synergy and Antagonism of Macroautophagy and Chaperone-Mediated Autophagy in a Cell Model of Pathological Tau Aggregation. Autophagy, 6, 182-183. https://doi.org/10.4161/auto.6.1.10815 |
| [48] | Sorrentino, V., Romani, M., Mouchiroud, L., Beck, J.S., Zhang, H., D’Amico, D., et al. (2017) Enhancing Mitochondrial Proteostasis Reduces Amyloid-β Proteotoxicity. Nature, 552, 187-193. https://doi.org/10.1038/nature25143 |
| [49] | Fang, E.F., Hou, Y., Palikaras, K., Adriaanse, B.A., Kerr, J.S., Yang, B., et al. (2019) Mitophagy Inhibits Amyloid-β and Tau Pathology and Reverses Cognitive Deficits in Models of Alzheimer’s Disease. Nature Neuroscience, 22, 401-412. https://doi.org/10.1038/s41593-018-0332-9 |
| [50] | Wild, E.J. and Tabrizi, S.J. (2014) Targets for Future Clinical Trials in Huntington’s Disease: What’s in the Pipeline? Movement Disorders, 29, 1434-1445. https://doi.org/10.1002/mds.26007 |
| [51] | Qi, L., Zhang, X., Wu, J., Lin, F., Wang, J., DiFiglia, M., et al. (2012) The Role of Chaperone-Mediated Autophagy in Huntingtin Degradation. PLOS ONE, 7, e46834. https://doi.org/10.1371/journal.pone.0046834 |
| [52] | Bauer, P.O., Goswami, A., Wong, H.K., Okuno, M., Kurosawa, M., Yamada, M., et al. (2010) Harnessing Chaperone-Mediated Autophagy for the Selective Degradation of Mutant Huntingtin Protein. Nature Biotechnology, 28, 256-263. https://doi.org/10.1038/nbt.1608 |
| [53] | Li, Z., Wang, C., Wang, Z., Zhu, C., Li, J., Sha, T., et al. (2019) Allele-Selective Lowering of Mutant HTT Protein by HTT-LC3 Linker Compounds. Nature, 575, 203-209. https://doi.org/10.1038/s41586-019-1722-1 |
| [54] | Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., et al. (2006) Suppression of Basal Autophagy in Neural Cells Causes Neurodegenerative Disease in Mice. Nature, 441, 885-889. https://doi.org/10.1038/nature04724 |
