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All Journal Jurnal Biotek Medisiana Indonesia The Indonesian Biomedical Journal Acta Biochimica Indonesiana Majalah Patologi Indonesia Jurnal Biomedika dan Kesehatan Majalah Sainstekes Jurnal Health Sains Muhammadiyah Journal of Geriatric eJournal Kedokteran Indonesia
Jusman, Sri Widia Azraki
Universitas Indonesia
Biochemistry, Genetics & Molecular Biology Computer Science & IT Dentistry Economics, Econometrics & Finance Health Professions Immunology & microbiology Law, Crime, Criminology & Criminal Justice Medicine & Pharmacology Neuroscience Nursing Public Health Veterinary

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Proteostasis disruption under hypoxia: therapeutic targets in cancer and neurodegenerative diseases Rahmiyati, Susi; Prijanti, Ani Retno; Jusman, Sri Widia A; Dewi, Syarifah
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 Abdul Halim Agus Setiyono Ahmad Aulia Andriani Andriani Angelina Stevany Regina Masengi Ani Retno Prijanti Deasyka Yastani Desdiani Dewi Sukmawati Ernie Purwaningsih Fanny Septiani Farhan Frans Ferdinal H, Novi Silvia Heri Wibowo Iris Rengganis Lailan Safina Nasution Lio, Tiara Mayang Pratiwi Mohamad Sadikin Mohamad Saekhu Mohammad Sadikin Ninik Mudjihartini Nurhadi Ibrahim Nurjati Chairani Siregar Putri C. Eyanoer Rahmiyati, Susi Retno Kuntarti Samsuridjal Djauzi Saptuti Chunaeni, Saptuti Sarsanti, Pungguri Ayu Nega Satriotomo, Irawan Sri Sukmaniah Suradi Syarifah Dewi Wardaya Wardaya Wawaimuli Arozal Wawan Mulyawan Wawan Mulyawan Werdhasari, Asri Wido Sari Nawangsih, Idah