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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.
Regenerative Roles of the Cyclooxygenase-2 Pathway in Neovascularization and Stem Cell Regulation: A Brief Perspective from In Vitro and In Vivo Studies Puspadewi, Melati; Dewi, Syarifah
Biomedical Journal of Indonesia Vol. 12 No. 1 (2026): Vol 12, No 1, 2026 (In Press)
Publisher : Fakultas Kedokteran Universitas Sriwijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32539/bji.v12i1.288

Abstract

Cyclooxygenase-2 (COX-2) is a key enzyme in prostanoid production and is best known as a mediator of the inflammatory response. Beyond this well-established role, COX-2 also contributes to tissue regeneration by promoting neovascularization and supporting stem cell recruitment, proliferation, and differentiation. Despite this, research on harnessing the COX-2 pathway as a therapeutic tool, rather than solely as a target for inhibition, remains limited, presenting a promising avenue for future studies. In this review, we summarize current insights from both in vitro and in vivo models into COX-2 signaling in tissue regeneration, focusing on molecular mechanisms through which its downstream mediators, especially prostaglandin (PGE2), regulate vascular formation, tissue growth, and stem cell function. We also briefly outline the dual nature of these processes, which can either facilitate repair or drive pathological outcomes, and discuss emerging strategies for achieving controlled therapeutic applications.