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All Journal Health Science Journal of Indonesia Molecular and Cellular Biomedical Sciences (MCBS) Indonesian Journal of Biotechnology and Biodiversity Acta Biochimica Indonesiana Eksakta : Berkala Ilmiah Bidang MIPA Makara Journal of Science
Syarifah Dewi
Department Of Biochemistry And Molecular Biology, Faculty Of Medicine, Universitas Indonesia, Jakarta
Agriculture, Biological Sciences & Forestry Astronomy Biochemistry, Genetics & Molecular Biology Chemical Engineering, Chemistry & Bioengineering Chemistry Civil Engineering, Building, Construction & Architecture Computer Science & IT Dentistry Energy Engineering Environmental Science Health Professions Immunology & microbiology Materials Science & Nanotechnology Mathematics Mechanical Engineering Medicine & Pharmacology Neuroscience Nursing Public Health Other

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Proteostasis disruption under hypoxia: therapeutic targets in cancer and neurodegenerative diseases Susi Rahmiyati; Ani Retno Prijanti; Sri Widia A Jusman; Syarifah Dewi
Acta Biochimica Indonesiana Vol. 8 No. 2 (2025): Acta Biochimica Indonesiana
Publisher : Indonesian Society for Biochemistry and Molecular Biology

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32889/actabioina.142

Abstract

Proteostasis, the integrated network regulating protein synthesis, folding, trafficking, and degradation, is essential for cellular function and organismal health. Reduced oxygen availability disrupts proteostasis through increased reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, impaired ATP-dependent protein folding, and altered chaperone expression. In cancer, tumor cells exploit chronic unfolded protein response (UPR) signaling to enhance survival, angiogenesis, and therapeutic resistance. Inhibition of IRE1α and PERK pathways has shown efficacy in preclinical models, though clinical translation faces challenges including off-target toxicity. In neurodegenerative diseases—Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis—chronic hypoxia accelerates protein aggregate accumulation through oxidative modifications and impaired autophagy-lysosome function. Therapeutic strategies targeting γ-secretase, BACE1, and protein clearance pathways have demonstrated limited clinical success despite mechanistic rationale. Understanding hypoxia-induced proteostasis failure may inform therapeutic development, though significant obstacles remain in translating preclinical findings to effective treatments for cancer and neurodegenerative diseases.
Co-Authors Ahmad, Nouman Albertus Raditya Danendra Alexander Rafael Satyadharma Alyssa Shafa Andiana Ani Retno Prijanti Dewi, Yulia Ratna Eziefule, Oluebube Magnificient Febriana Catur Iswanti Melva Louisa Milya Urfa Ahmad Mohamad Sadikin Mohamad Sadikin Muchlis Ramli Muhammad Faruqi Nabillah, Deya Adiby Nafrialdi Nafrialdi Ni Made Wiasty Sukanty Puspita Eka Wuyung Reni Paramita Septelia I. Wanandi Septelia Inawati Wanandi SEPTELIA INAWATI WANANDI Sri W.A. Jusman Sri Widia A Jusman Susi Rahmiyati Vivian Soetikno Wardaya Wawaimuli Arozal Wawan Mulyawan