Balancing act: navigating the intricacies of proteostasis

Authors

  • Manisha Shukla Department of Biotechnology, Pandit S.N. Shukla University Shahdol, Madhya Pradesh, India
  • Mohammad Abdul Ahad Department of Biotechnology, Pandit S.N. Shukla University Shahdol, Madhya Pradesh, India

DOI:

https://doi.org/10.18203/2320-6012.ijrms20242251

Keywords:

Cancer, Neurodegenerative diseases, Proteostasis, Therapeutic strategies, Ubiquitin-proteasome system

Abstract

Proteostasis, the intricate balance of protein synthesis, folding, trafficking, and degradation, is a fundamental cellular process crucial for maintaining cellular health and homeostasis. Imbalances in proteostasis are implicated in various diseases, including neurodegenerative disorders, cancer, aging, type 2 diabetes mellitus, cataract, huntington's disease, heart disease, sarcopenia, ischemic disorders, diabetic neuropathy and other metabolic conditions. We delve in to the proteostasis mechanisms and highlight the significance of proteostasis in the context of protein misfolding diseases that have broadened our understanding of proteostasis network. Further, we explore the relevance of proteostasis in cancer, shedding light on the interplay between the ubiquitin-proteasome system and oncoproteins. Furthermore, we also address therapeutic approaches aimed at modulating proteostasis to combat protein misfolding diseases. The mysteries of protein balance continue to captivate researchers, and the evolving landscape of proteostasis research promises insights into novel therapeutic strategies and a deeper understanding of its role in human health. This review offers a comprehensive perspective on the ever-expanding frontiers of proteostasis research, with the hope of inspiring further exploration and innovation in this dynamic field.

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References

Bekker D, Jensen B. An Optimized Shotgun Strategy for the Rapid Generation of Comprehensive Human Proteomes. Cell Syst. 2017;4(6):587-99.

Whittemore SR, Ohri S, Forston MD, Wei GZ, Hetman M. The Proteostasis Network: A Global Therapeutic Target for Neuroprotection after Spinal Cord Injury. Cells. 2022;11:21.

Dissmeyer N, Coux O, Rodriguez MS, Barrio R. PROTEOSTASIS: A European Network to Break Barriers and Integrate Science on Protein Homeostasis. Trends in Biochemical Sciences. 2019;44(5):383-7.

Powers ET, Balch WE. Diversity in the origins of Proteostasis networks-a driver for protein function in evolution. Nature Reviews Molecular Cell Biol. 2013;14(4):237-48.

Jayaraj GG, Hipp MS, Ulrich Hartl FU. Functional modules of the proteostasis network. Cold Spring Harb Perspect Biol. 2020;12:339-51.

Hartl FU, Bracher A, Hayer-Hartl M. Molecular chaperones in protein folding and proteostasis. Nature. 2019;475:324-32.

Díaz-Villanueva JF, Díaz-Molina R, and V. García-González. Protein folding and mechanisms of proteostasis. Int J Molecular Sci. 2015;16(8):17193-230.

Balchin D, Hayer-Hartl M, Ulrich Hartl F. In vivo aspects of protein folding and quality control. 2016:1-22.

Finley D. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annual Rev Biochem. 2009;78:477-513.

Enam C, Geffen Y, Ravid T, Gardner RG. Protein Quality Control Degradation in the Nucleus. Biochem. 2018;10:1146.

Yang Z, Klionsky DJ. Mammalian autophagy: Core molecular machinery and signaling regulation. Current Opinion in Cell Biology. 2010;22(2):124-31.

Massey AC, Zhang C, Cuervo AM. Chaperone‐Mediated Autophagy in Aging and Disease. Curr Top Dev Biol. 2006:73:205-35.

Jaisson S, Gillery P. Impaired proteostasis: Role in the pathogenesis of diabetes mellitus. Diabetologia. 2014;57(8):1517-27.

Venkatesh S, Lee J, Singh K, Lee I, Suzuki CK. Multitasking in the mitochondrion by the ATP-dependent Lon protease. Biochimica et Biophysica Acta - Molecular Cell Res. 2012;1823(1):56-66.

Adams CJ, Kopp MC, Larburu N, Nowak PR, Ali MMU. Structure and molecular mechanism of ER stress signaling by the unfolded protein response signal activator IRE1. Front Mol Biosci. 2019;12:6:11.

Xu D, Liu Z, Liang MX, Fei YJ, Zhang W, Wu Y, et al. Endoplasmic reticulum stress targeted therapy for breast cancer. Cell Communication Signaling. 2022;20:174.

Ajmal MR. Protein Misfolding and Aggregation in Proteinopathies: Causes, Mechanism and Cellular Response. Diseases. 2023;11(1).

Deture MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Molecular Neurodegeneration. 2019;14(1).

Thellung S, Corsaro A, Dellacasagrande I, Nizzari M, Zambito M, Florio T. Proteostasis unbalance in prion diseases: Mechanisms of neurodegeneration and therapeutic targets. Front Neurosci. 2022;16:966019.

Hartl FU. Protein Misfolding Diseases. Annu Rev Biochem. 2017:86:21-6.

Marrano N, Biondi G, Borrelli A, Rella M, Zambetta T, Gioia LD, et al. Type 2 Diabetes and Alzheimer’s Disease: The Emerging Role of Cellular Lipotoxicity. Biomolecules. 2023;13(1):183.

Pevzner Y, Metcalf R, Kantor M, Sagaro D, Daniel K. Recent advances in proteasome inhibitor discovery. Expert Opinion on Drug Discovery. 2013;8(5):537-68.

Bixby D, Kujawski L, Wang S, Malek SN. The pre-clinical development of MDM2 inhibitors in chronic lymphocytic leukemia uncovers a central role for p53 status in sensitivity to MDM2 inhibitor-mediated apoptosis. Cell Cycle, Taylor and Francis Inc. 2008;7:971-9.

Fricker LD. Proteasome Inhibitor Drugs. Annu Rev Pharmacol Toxicol. 2020:60:457-76.

Jayaweera SPE, Kanakanamge SPW, Rajalingam D, Silva GN. Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma. Frontiers Oncol. 2021;11.

Rajan AM, Kumar S. New investigational drugs with single-agent activity in multiple myeloma. Blood Cancer J. 2016;6(7):2016.

Luo W, W Sun, Taldone T, Rodina A, Chiosis G. Open Access REVIEW Heat shock protein 90 in neurodegenerative diseases. Mol Neurodegeneration. 2010;5:24.

Xu J, Xie R, Liu X, Wen G, Jin H, Yu Z, et al. Expression and functional role of vacuolar H+-ATPase in human hepatocellular carcinoma. Carcinogenesis. 2012;33(12):2432-40.

Wu YC, Wu WKK, Li Y, Yu L, Li ZJ, Wong CCM, et al. Inhibition of macroautophagy by bafilomycin A1 lowers proliferation and induces apoptosis in colon cancer cells. Biochem Biophys Res Commun. 2009;382(2):451-6

Ashrafizadeh M, Paskeh MDA, Mirzaei S, Gholami MH, Zarrabi A, Hashemi F, et al. Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response. J Exp Clin Cancer Res. 2022;41:105.

Bhattacharya D, Mukhopadhyay M, Bhattacharyya M, Karmakar P. Is autophagy associated with diabetes mellitus and its complications? A review. EXCLI J. 2018;17:709-20.

Kim DH, Rossi JJ. Strategies for silencing human disease using RNA interference. Nature Reviews Genet. 2007;8(3):173-84.

Ahmad I. CRISPR/Cas9 A Promising Therapeutic Tool to Cure Blindness: Current Scenario and Future Prospects. Int J Molecular Sci. 2022;23(19).

Oikonomou V. Autophagy and LAP in the fight against fungal infections: Regulation and therapeutics. Mediators of Inflammation. 2018. Hindawi Limited, 2018.

Nam SM, Jeon YJ. Proteostasis in the endoplasmic reticulum: Road to cure. Cancers, MDPI. 2019.

Brancolini C, Iuliano L. Proteotoxic stress and cell death in cancer cells. Cancers. 2020;12:9.

Valenzuela V, Jackson KL, Sardi SP, Hetz C. Gene Therapy Strategies to Restore ER Proteostasis in Disease. Molecular Therapy. 2018;26(6):1404-13.

Chen JH, Wu CH, Chiang CK. Therapeutic approaches targeting proteostasis in kidney disease and fibrosis. Int J Molecular Sci. 2021;22:16.

Chen W, Hu Y, Ju D. Gene therapy for neurodegenerative disorders: advances, insights and prospects. Acta Pharmaceutica Sinica B. Acta Pharm Sin B. 2020;10(8):1347-59.

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Published

2024-07-31

How to Cite

Shukla, M., & Ahad, M. A. (2024). Balancing act: navigating the intricacies of proteostasis. International Journal of Research in Medical Sciences, 12(8), 3091–3099. https://doi.org/10.18203/2320-6012.ijrms20242251

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Section

Review Articles